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Tham T Le,1 David B Price,2– 4 Clement Erhard,5 Bill Cook,6 Anna Quinton,7 Rohit Katial,8 George C Christoff,9 Luis Perez-de-Llano,10 Alan Altraja,11,12 Celine Bergeron,13 Arnaud Bourdin,14 Mariko Siyue Koh,15,16 Lauri Lehtimäki,17,18 Bassam Mahboub,19 Nikolaos G Papadopoulos,20,21 Paul Pfeffer,22,23 Chin Kook Rhee,24 Victoria Carter,2,3 Neil Martin,25,26 Trung N Tran1 On behalf of the EVEREST Study Working Group1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Optimum Patient Care Global, Cambridge, UK; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 7BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 9Faculty of Public Health, Medical University Sofia, Sofia, Bulgaria; 10Department of Respiratory Medicine, University Hospital Lucus Augusti, Lugo, Spain; 11Department of Pulmonology, University of Tartu, Tartu, Estonia; 12Lung Clinic, Tartu University Hospital, Tartu, Estonia; 13Centre for Lung Health, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; 14PhyMedExp, University of Montpellier, CNRS, INSERM, University Hospital of Montpellier, Montpellier, France; 15Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore; 16Duke-NUS Medical School, Singapore; 17Allergy Centre, Tampere University Hospital, Tampere, Finland; 18Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 19Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 20Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 21Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 22Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 23Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 24Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 25Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 26University of Leicester, Leicester, UKCorrespondence: Trung N Tran, BioPharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA, Email trung.tran1@astrazeneca.comIntroduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.Methods: This was a historical cohort study of patients with severe asthma (aged ≥ 18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled.Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively.Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment.Keywords: biologic, disease burden, healthcare resource utilization, severe asthma

Joon Young Choi,1 Chin Kook Rhee2 1Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Chin Kook Rhee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Tel +82 2 2258 6067, Fax +82 2 599 3589, Email chinkook77@gmail.comAbstract: Asthma is a chronic inflammatory airway disease with significant burden; exacerbations can severely affect quality of life and healthcare costs. Advances in big data analysis and artificial intelligence have made it easier to predict future exacerbations more accurately. This study used an integrated dataset of Korean National Health Insurance, meteorological, air pollution, and viral data from national public databases to develop a model to predict asthma exacerbations on a daily basis in South Korea. We merged these sources and applied random forest, AdaBoost, XGBoost, and LightGBM machine learning models to compare their performances at predicting future exacerbations. Of the models, XGBoost (AUROC of 0.68 and accuracy of 0.96) and LightGBM (AUROC of 0.67 and accuracy of 0.96) were the most promising. Common important variables were the number of visits and exacerbations per year, and medical resource utilization, including the prescription of asthma medications. Comorbid diabetes, hypertension, gastroesophageal reflux, arthritis, metabolic syndrome, osteoporosis, and ischemic heart disease were also associated with elevated exacerbation risk. The models examined in this study highlight the importance of previous exacerbations, use of medical resources, and comorbidities in the prediction of future exacerbations in patients with asthma.Keywords: asthma, machine learning, big data analysis, South Korea, XGBoost, LightGBM

Kwang Yong Choi,1 Hwan Il Kim,1 Chin Kook Rhee,2 Kwang Ha Yoo,3 Yong Bum Park,4 Youlim Kim,3 So Eun Lee,5 Jung-Ae Kim,6 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 5Respiratory, Medical Affairs, Boehringer-Ingelheim Korea, Seoul, Republic of Korea; 6Real-World Solutions, IQVIA Korea, Seoul, Republic of KoreaCorrespondence: Yong Il Hwang, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, Republic of Korea, Email hyicyk@hallym.or.kr; hyicyk@gmail.comBackground: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation.Methods: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period.Results: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10– 1.26, p< 0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13– 1.35, p< 0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p< 0.0001).Conclusion: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroids, long-acting beta-2 agonists, long-acting muscarinic receptor antagonists, medical cost

Eun Kyung Kim,1,&ast; Eunyoung Lee,2,&ast; Ji Eun Park,3,&ast; Jae Seung Lee,4 Hye Sook Choi,5 Bumhee Park,6,7 Seung Soo Sheen,3 Kwang Joo Park,3 Chin Kook Rhee,8 Sang Yeub Lee,9 Kwang Ha Yoo,10 Joo Hun Park3 1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Neurology, McGovern Medical School at UTHealth, Houston, TX, USA; 3Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea; 4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 6Office of Biostatistics, Medical Research Collaborating Center, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea; 7Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea; 8Department of Internal Medicine, Seoul St. Mary’s Hospital, Catholic University of Korea, Seoul, Republic of Korea; 9Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea; 10Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Joo Hun Park, Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Worldcup Road 164, Suwon, Gyeonggi-do, 16499, Republic of Korea, Tel +82-31-219-5116, Fax +82-31-219-5124, Email jhpamc@naver.com; jhpamc@hanmail.netBackground: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities.Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174).Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04– 1.43), heart failure (HR: 1.45, 95% CI: 1.14– 1.84), arrhythmia (HR: 1.72, 95% CI: 1.41– 2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64– 3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05).Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.Keywords: COPD, inhaler therapy, cardiovascular event, comorbidities

Yune-Young Shin,1,&ast; Sojung Park,1,&ast; Kyung Joo Kim,2 Chin Kook Rhee,2 Kwang Ha Yoo,3 Ki-Suck Jung,4 Jin Hwa Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 4Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Gyeonggi-do, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Hwa Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil Gangseo-gu, Seoul, 07804, Republic of Korea, Tel +82 2 6986 1631, Fax +82 2-2655-2076, Email jinhwalee@ewha.ac.krPurpose: To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm).Patients and Methods: We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD).Results: A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm.Conclusion: Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.Keywords: emergency department, hospitalization, lung function, restrictive lung disease, wheezing

Ji Won Park,1,&ast; Yoonki Hong,2,&ast; Chin Kook Rhee,3 Hye Sook Choi,4 Kyungjoo Kim,3 Kwang Ha Yoo,5 Ki-Suck Jung,6 Joo Hun Park1 1Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea; 2Department of Internal Medicine, Kangwon National University, Chuncheon, South Korea; 3Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 4Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, South Korea; 5Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea; 6Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea&ast;These authors contributed equally to this workCorrespondence: Joo Hun Park, Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Worldcup road 164, Suwon, Gyeonggi-do, 16499, South Korea, Tel +82-31-219-5116 ; +82-10-8379-8299, Fax +82-31-219-5124, Email jhpamc@naver.com; jhpamc@hanmail.netBackground: A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world.Methods: We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years).Results: Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P< 0.05). Hospitalization due to respiratory causes was also higher among ICS users (P< 0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P< 0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P< 0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P< 0.05).Conclusion: Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.Keywords: COPD, inhaled corticosteroids, pneumonia, mortality

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Stephanie Chen,1 Marc Miravitlles,2 Chin Kook Rhee,3 Ian D Pavord,4 Rupert Jones,5 Victoria Carter,6 Benjamin Emmanuel,1 Marianna Alacqua,7 David B Price6,8 1BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA; 2Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 3College of Medicine, Seoul St Mary’s Hospital, the Catholic University of Korea, Seoul, South Korea; 4Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 5Faculty of Health, University of Plymouth, Plymouth, UK; 6Observational and Pragmatic Research Institute, Singapore, Singapore; 7BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Cambridge, UK; 8Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, Singapore, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Some patients with chronic obstructive pulmonary disease (COPD) experience frequent exacerbations despite maximal inhaled therapy (“triple therapy”), possibly leading to high health care resource utilization (HCRU).Aim: Describe characteristics, future HCRU, and mortality of patients with COPD who experience frequent exacerbations despite triple therapy; characterize individuals who may be candidates for biologic therapies.Methods: This descriptive observational study used primary care data of patients aged ≥ 40 years in the United Kingdom receiving maintenance therapy for COPD who had ≥ 1 year of data prior to index date and ≥ 1 year of follow-up data. We described these patients’ clinical and demographic characteristics, including blood eosinophil counts (BEC), pattern of exacerbations, hospitalizations, and corticosteroid exposure, as well as future exacerbations, hospitalizations, and death.Results: Of 43,753 patients with maintenance-treated COPD, 6480 experienced exacerbations despite ≥ 3 months of triple therapy. Of these, 5669 had available BEC: 1287 (22.7%) had BEC ≥ 250 cells/μL and ≥ 3 exacerbations in the year prior to the index date; 471 (36.6%) received ≥ 4 acute courses of oral corticosteroids. Patients with a pattern of high disease burden continued to have high disease burden: 51.1% experienced ≥ 3 exacerbations and 2.6% experienced ≥ 3 hospitalizations. Patients who experienced exacerbations despite triple therapy had a significantly higher risk of COPD-related death than other maintenance-treated patients (5.8% vs 2.1%).Conclusion: Nearly one-quarter of patients receiving triple therapy for COPD who experienced frequent exacerbations had elevated BEC and ≥ 3 exacerbations, suggesting a potential mechanism of persistent eosinophilic inflammation that could be a target for eosinophil-depleting biologic therapy.Keywords: chronic obstructive pulmonary disease, disease burden, eosinophils, exacerbations, health care resource utilization

Sunyoung Kim,1 Hyoung Kyu Yoon,2 Chin Kook Rhee,3 Hee-Won Jung,4 Hyun Lee,5 Yong Suk Jo3 1Department of Family Medicine, College of Medicine, Kyung Hee University, Seoul, Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 4Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 5Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, KoreaCorrespondence: Yong Suk Jo, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Tel +82-2-2258-6067, Fax +82-2-599-3589, Email lucidyonge@gmail.comBackground and Objective: Sarcopenia is mainly results from aging; however, it is more prevalent in chronic airway disease such as obstructive pulmonary disease (COPD). Hand grip strength (HGS) can be used as an indicator to evaluate sarcopenia. We aimed to assess the association between HGS and severity of airflow limitation (AFL) in the general population.Methods: We conducted a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2018. Subjects aged ≥ 40 years who underwent both spirometry and HGS tests were included. AFL was defined by spirometry revealed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70). A propensity score-matched comparison was performed, and the risk for moderate-to-very severe AFL was analyzed using logistic regression analysis.Results: Among 15,950 subjects, 2277 (14.3%) had AFL with mean FEV1 was 77.1% of the predicted value. Male was predominant in both individuals without AFL and with AFL (74.2% vs 73.5%, p = 0.613). The HGS was 32.9 ± 9.5 kg and 33.3 ± 9.5 kg in participants without AFL and with AFL (p = 0.109). However, HGS was significantly decreased as AFL getting more severe: 34.0 ± 9.6 kg in mild, 33.0 ± 9.5 kg in moderate, and 30.8 ± 8.5 kg in severe to very severe AFL group (p< 0.001). As HGS decreased, adjusted odds for moderate-to-very severe AFL increased compared to those with mild AFL (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.951– 0.987) and both without AFL and mild AFL group (aOR, 0.98; 95% CI, 0.967– 0.995) in age-, sex-, and body mass index (BMI)-matched comparisons.Conclusion: Lower HGS is significantly associated with moderate-to-very severe AFL in age-, sex-, and BMI-matched comparisons.Keywords: hand grip strength, airflow limitation, severity

Tai Joon An,1 Yeun Jie Yoo,2 Jeong Uk Lim,1 Wan Seo,3 Chan Kwon Park,1 Chin Kook Rhee,4 Hyoung Kyu Yoon1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Rehabilitation Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea; 3Department of Internal Medicine, St. Peter’s Hospital, Seoul, Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, KoreaCorrespondence: Hyoung Kyu Yoon Tel +82 2-3779-2213Email cmcyhg@gmail.comBackground: Evaluating the diaphragm muscle in chronic obstructive pulmonary disease (COPD) is important. However, the role of diaphragm ultrasound (DUS) in distinguishing the exacerbation status of COPD (AECOPD) is not fully understood. We set this study to evaluate the role of DUS as a biomarker for distinguishing the AECOPD.Methods: COPD patients who underwent DUS were enrolled between March 2020 and November 2020. The diaphragm thickening fraction (TFmax) and diaphragm excursion (DEmax) during maximal deep breathing were measured. Patients were divided into exacerbation and stable groups. Demographics, lung function, and DUS findings were compared between the two groups. Receiver operating characteristic curve and univariate/multivariate logistic regression analyses were performed.Results: Fifty-five patients were enrolled. The exacerbation group had a lower body mass index (BMI) (20.9 vs 24.2, p = 0.003), lower TFmax (94.8 ± 8.2% vs 158.4 ± 83.5%, p = 0.010), and lower DEmax (30.8 ± 11.1 mm vs 40.5 ± 12.5 mm, p = 0.007) compared to stable group. The areas under the TFmax (0.745) and DEmax (0.721) curves indicated fair results for distinguishing AECOPD. The patients were divided into low and high TFmax and DEmax groups based on calculated cut-off values. Low TFmax (odds ratio [OR] 8.40; 95% confidence interval [CI] 1.55– 45.56) and low DEmax (OR 11.51; 95% CI 1.15– 115.56) were associated with AECOPD after adjusting for age, sex, BMI, and lung functions.Conclusion: DUS showed the possibility of an imaging biomarker distinguishing AECOPD from stable status.Keywords: COPD, exacerbation, diaphragm, ultrasound, biomarker

Yong Suk Jo,1,2 Kwang Ha Yoo,3 Yong Bum Park,1,2 Chin Kook Rhee,4 Ki Suck Jung,2,5 Seung Hun Jang,2,5 Ji Young Park,2,5 Youlim Kim,2,6 Bo Yeon Kim,7 Sang In Ahn,7 Yon U Jo,7 Yong Il Hwang2,5 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 2Lung Research Institute of Hallym University College of Medicine, Chuncheon, South Korea; 3Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; 6Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon-Si, Gangwon-Do, Korea; 7Health Insurance Review & Assessment Service, Wonju, Republic of KoreaCorrespondence: Yong Il Hwang Tel +82-31-380-3715Fax +82-31-380-3973Email hyicyk@hallym.or.krBackground and Objective: Maintaining adequacy in chronic obstructive pulmonary disease (COPD) care is essential to sustain an adequate level of care. We aimed to assess the current status of COPD quality control and the influence of inhaler changes on disease-related health care utilization.Methods: The Health Insurance Review and Assessment Service (HIRA) nationwide database for reimbursed insurance claims from all medical institutions in South Korea from May 2014 to April 2017 was investigated. COPD care quality was assessed by the performance rate of spirometry, the percentage of persistent visit patients and patients prescribed a bronchodilator. The number of severe exacerbations was evaluated.Results: A total of 68,942 COPD patients were included for 3 years of longitudinal analyses. The overall spirometry enforcement rate was just over 50%, the percentage of regular follow-up patients was over 85%, and bronchodilators were prescribed to over 80% of the patients. COPD-related hospitalization or ER visit rates were 16.6%, 15.3%, and 17.8% for three consequent assessments, respectively. Inhaler changes were analyzed between the first and second assessments: 57.1% were maintained, 0.4% were changed to another class, 9% were escalated, and 5.2% were de-escalated. Only in the escalated group, especially those who changed from the mono to dual inhaler and dual to triple inhaler, had fewer hospitalizations or ER visits.Conclusion: Adequacy of COPD care status was not that high considering the low-enforcement rate of spirometry, but most patients were prescribed a bronchodilator and regularly followed up. Those who escalated inhaler treatment experienced less health care utilization.Keywords: COPD, population-based, quality assessment, inhaler, health care utilization

Hye Sook Choi,1 Chin Kook Rhee,2 Yong Bum Park,3,4 Kwang Ha Yoo,5 Seong Yong Lim6 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kyung Hee Medical Center, Seoul, South Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, Seoul, South Korea; 3Lung Research Institute of Hallym University College of Medicine, Chuncheon, South Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, South Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, South Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South KoreaCorrespondence: Seong Yong LimDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul 06652, South KoreaTel +82-2-2001-2493Fax +82-2-2001-1596Email mdlimsy@skku.eduBackground: Metabolic syndrome (MetS) is a well-known comorbidity of chronic obstructive pulmonary disease (COPD). However, their interrelationship, particularly in early COPD, remains unclear. Therefore, we aimed to assess the prevalence and clinical characteristics of MetS in patients with early COPD, and to explore the impact of MetS on the frequency of COPD exacerbations and associated medical costs.Patients and methods: We retrospectively enrolled 43,874 subjects from the KNHANES, including 2164 patients with early COPD (≥40 years old), recorded smoking history, and Global Initiative for Chronic Obstructive Lung Disease spirometric grade I or II, with data linked to the NHI database. We extracted and analyzed data regarding health-care utilization and medical costs for 5 years (2007 to 2012).Results: Among 2164 patients with early COPD, the prevalence of MetS was 31.2%, and it was higher in women than in men (35.1% vs. 26.6%; P

Jeong Uk Lim,1 Eun Kyung Kim,2 Seong Yong Lim,3 Jin Hwa Lee,4 Jae Seung Lee,5 Sang-Do Lee,5 Yeon-Mok Oh,5 Chin Kook Rhee1 On behalf of the KOLD Study Group1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, South Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea; 5Department 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 KoreaCorrespondence: Chin Kook RheeDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero Seocho-gu, Seoul 06591, Republic of KoreaTel +82-2-2258-6067Fax +82-2-599-3589Email chinkook77@gmail.comObjective: The presence of both emphysema and airway wall thickening determined via volumetric computed tomography (CT) is defined as mixed phenotype. The long-term clinical course of this phenotype has not been studied in depth. This study compared the mixed phenotype to other phenotypes of chronic obstructive pulmonary disease (COPD) patients.Methods: COPD patients enrolled in the Korean Obstructive Lung Disease (KOLD) study from June 2005 to October 2015 were evaluated. The emphysema index and the percentage of bronchial mean wall area were calculated from volumetric CT scans. Patients with COPD were classified into four phenotypes using two cutoffs: emphysema index of 15% and median value of mean wall area (MWA%).Results: Of 435 patients with COPD, 99 (22.8%) were defined as CT-normal type, 119 (27.4%) as emphysema-dominant type, 113 (26.0%) as airway-dominant type, and 104 (23.9%) as mixed type. The mixed phenotype showed the highest baseline total COPD Assessment Test (CAT) and St. George’s Respiratory Questionnaire (SGRQ) scores. Moreover, it had the highest proportion of patients experiencing exacerbation of COPD (50.0%), and had the lowest baseline FEV1. Lower BMI, GOLD stages III–IV, and mixed phenotype were significant factors associated with severe exacerbation frequency in univariate analyses. Multivariate analyses showed that lower BMI and CT phenotype were significant factors associated with severe exacerbation frequency. Compared to the CT-normal phenotype, the mixed phenotype was significantly associated with more frequent severe exacerbation (IRR 4.134, 95% CI: 1.135–15.057, P=0.031).Conclusion: Patients with mixed phenotype are more symptomatic, have poorer pulmonary function, and are associated with more frequent severe exacerbation.Keywords: COPD, emphysema, computed tomography, mixed phenotype

Joon Young Choi,1 Hyoung Kyu Yoon,2 Kyeong-Cheol Shin,3 So-Young Park,4 Chang Youl Lee,5 Seung Won Ra,6 Ki Suck Jung,7 Kwang Ha Yoo,4 Chang-Hoon Lee,8 Chin Kook Rhee9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonology and Allergy, Regional Center for Respiratory Disease, Yeungnam University Medical Center, Daegu, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 7Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Chin Kook RheeDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul 06591, Republic of KoreaTel +82 2 2258 6067Fax +82 2 599 3589Email chinkook77@gmail.comPurpose: Previous studies have used various definitions to classify chronic obstructive pulmonary disease (COPD) patients into chronic bronchitis (CB) and non-CB patients. This study was performed to identify differences among three definitions of CB based on the classical method, St. George’s Respiratory Questionnaire (SGRQ), and the CAT (COPD Assessment Test) score.Patients and methods: We extracted data from the multicenter Korea COPD Subgroup Study (KOCOSS) cohort, for which patients recruited from among 47 medical centers in South Korea beginning in April 2012. Patients were classified according to three different definitions of CB: 1) classical definition; 2) SGRQ (using questions regarding cough and sputum); and 3) CAT score (comprising cough [CAT1] and sputum [CAT2] subscale scores).Results: A total of 2694 patients were enrolled in this study. The proportions of CB were 10.8%, 35.8%, and 24.0% according to the classical, SGRQ, and CAT definitions, respectively. The three definitions yielded consistently significant differences between CB and non-CB patients in modified Medical Research Council dyspnea scale CAT score, SGRQ score, number of moderate-to-severe exacerbations per year and forced expiratory volume in 1 second. By three definitions, CB consistently predicted future risk of exacerbation. The kappa coefficient of agreement between the classical definition and SGRQ definition was 0.29, that of the classical definition and CAT definition was 0.32, and that of the SGRQ definition and CAT definition was 0.44.Conclusion: Patients with CB according to the new definitions based on SGRQ or CAT score showed similar clinical characteristics to those defined according to the classical definition. The new CB definitions may be used as alternatives to the classical definition.Keywords: chronic bronchitis, CAT score, SGRQ score, chronic obstructive pulmonary disease, KOCOSS database

Jung-Kyu Lee,1 Chin Kook Rhee,2 Kyungjoo Kim,2 Seung Won Ra,3 Jae Ha Lee,4 Ki-Suck Jung,5 Kwang Ha Yoo,6 Yoo-Il Kim,7 Deog Kyeom Kim1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 4Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaCorrespondence: Deog Kyeom KimDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, #395 Shindaebang-2-Dong, Dongjak-Gu, Seoul 156-707, Republic of KoreaTel +82-2-870-2228Fax +82-2-831-0714Email kimdkmd@snu.ac.krBackground: Methylxanthines and leukotriene receptor antagonists (LTRA) are not a first-line medical treatment for chronic obstructive pulmonary disease (COPD) but are frequently prescribed despite limited evidence. We aimed to elucidate the real prescribing status and clinical impacts of these agents in early COPD patients.Methods: Patients with mild-to-moderate COPD (FEV1>50%) were selected from the Korean National Health and Nutrition Examination Survey data between 2007 and 2012. Besides analyzing the prescription status of methylxanthines and LTRA and the contributing factors to the prescription, we evaluated the clinical impacts of these drugs on the exacerbation, hospitalization, and medical costs.Results: Of 2269 patients with mild-to-moderate COPD, 378 patients (16.7%) were under medical treatments, and the users of methylxanthines and/or LTRA were 279 patients (12.3%); however, only 139 patients (6.1%) were inhaler users. The contributing factors for the prescription of methylxanthines were a comorbidity of asthma or allergic disease, poor lung function, low quality of life, prescribing doctor from the specialty of internal medicine, and an institution type of private hospital. The prescription of LTRA was associated with the comorbidity of allergic disease. The methylxanthine and/or LTRA users had more hospital utilization but did not have significant differences in acute exacerbations and medical cost for hospital utilization, compared with the non-users.Conclusion: Methylxanthines and LTRA were used in a significant proportion of patients with mild-to-moderate COPD in real fields without favorable impacts on the exacerbations, hospitalizations, or medical costs. The use of more effective inhaled medications should be encouraged.Keywords: pulmonary disease, chronic obstructive, methylxanthine, leukotriene antagonists, drug prescriptions

Jeong Uk Lim,1,* Chan Kwon Park,2,* Tae-Hyung Kim,3 An-Soo Jang,4 Yong Bum Park,5 Chin Kook Rhee,1 Ki Suck Jung,6 Kwang Ha Yoo,7 Won-Yeon Lee,8 Hyoung Kyu Yoon2 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 4Division of Respiratory and Allergy, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 8Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea*These authors contributed equally to this workCorrespondence: Hyoung Kyu YoonDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary`s Hospital, School of Medicine, The Catholic University of Korea, #62 Yeouido-dong, Yeongdeungpo-gu, Seoul 150-713, Republic of KoreaTel +82-2-3779-2213Fax +82-2-784-5458Email cmcyhg@catholic.ac.krObjectives: Depression is a major comorbidity that affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). COPD patients with depression are hospitalized more frequently, and show more acute exacerbations, decreased physical and social activities, and higher mortality compared to their non-depressed counterparts. In the present study, we investigated the clinical impact of depressive symptoms and associated clinical factors in Korean patients with COPD by evaluating multicenter cohort data.Materials and methods: Patients with COPD enrolled in the Korean COPD Subtype Study, a multicenter observational study, from December 2011 to October 2014 were selected for evaluation. The initial evaluation of all patients included pulmonary function tests, 6 min walk distance (6MWD), the COPD Assessment Test (CAT), and the COPD-specific version of the St. George’s Respiratory Questionnaire (SGRQ-C). Significant depression was defined as a Beck Depression Inventory-II (BDI-II) score ≥17.Results: Among the 270 study patients, 19.6% had significant depression. The depressed group showed a higher proportion of females (41.4%), lower body mass index (BMI), and lower education level compared to the non-depressed group (p = 0.002, p = 0.008, and p = 0.019, respectively). The depressed group had significantly higher CAT and SGRQ-C scores, as well as a lower 6MWD, compared to the non-depressed group based on 6 month-interval serial measurements over 3 years. The total SGRQ-C score and the symptoms, activity, and impact domain scores were significant predictors of depression (area under curves [AUCs] of 0.699 [0.613–0.786], 0.670 [0.581–0.758], 0.680 [0.589–0.770], and 0.689 [0.603–0.776], respectively). From CAT score domains, sleep and energy scores were significant predictors of depression (AUCs of 0.619 [0.522–0.715] and 0.595 [0.504–0.685], respectively). SGRQ-C score, low BMI, and decreased 6MWD were significantly associated with depression in a multivariable analysis.Conclusion: A considerable proportion of patients with COPD had depression, and a high SGRQ-C score, low BMI, and low 6MWD were significantly associated with depression. As improving quality of life in this subgroup is difficult, physicians should be more active in screening patients with significant depression.Keywords: association, COPD Assessment Test, depression, St. George’s Respiratory Questionnaire

Kyu Yean Kim,1 Marc Miravitlles,2,3 Pawel Sliwinski,4 Richard Costello,5 Victoria Carter,6,7 Jessica Tan,8 Therese Sophie Lapperre,8,9 Bernardino Alcazar,10 Caroline Gouder,11 Cristina Esquinas,2,12 Juan Luis García-Rivero,13 Anu Kemppinen,6 Augustine Tee,14 Miguel Roman-Rodríguez,15 Juan José Soler-Cataluña,3,16 David Price,6–7,17 Chin Kook Rhee11Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Pneumology Department, University Hospital Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 3CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 42nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 5Department of Respiratory Medicine, Royal College of Surgeons, Dublin, Ireland; 6Optimum Patient Care, Cambridge, UK; 7Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK; 8Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark; 9Singhealth Duke-NUS Medical Academic Clinical Programme, Duke-NUS Medical School, Singapore; 10Respiratory Department, Hospital de Alta Resolución de Loja, Madrid, Spain; 11Department of Respiratory Medicine, Mater Dei Hospital, L-Imsida, Malta; 12Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 13Hospital Comarcal de Laredo, Cantabria, Spain; 14Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore; 15Primary Health-care Center Son Pisà, IB-Salut, Palma, Spain; 16Pneumology Department, Hospital Arnau de Vilanova, Valencia, Spain; 17Observational and Pragmatic Research Institute, SingaporeAbstract: We aimed to compare clinical characteristics between Asian and Western chronic obstructive pulmonary disease (COPD) patients. This was a sub-analysis of an international, multicenter, prospective cohort study. Asian patients were enrolled in Singapore and South Korea. Western patients were enrolled in Spain, Poland, Ireland, the United Kingdom, and Malta. A total of 349 patients were analyzed. Among them, 110 (32%) patients were Asian and 239 (68%) Western. Male sex was more predominant in Asian than in Western (95% versus 63%, respectively; P

Jeong Uk Lim, Chang Dong Yeo, Chin Kook Rhee, Hye Seon Kang, Chan Kwon Park, Ju Sang Kim, Jin Woo Kim, Seung Joon Kim, Hyoung Kyu Yoon, Sang Haak LeeDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaObjectives: A significant proportion of non-small cell lung cancer (NSCLC) patients are never-smokers. However, the clinical impact of spirometrically diagnosed chronic obstructive pulmonary disease (COPD) on the prognosis of never-smoking NSCLC has not been evaluated in the context of treatment modalities and other cancer-related factors. In the present study, we evaluated the clinical impact of COPD in non-smoking NSCLC patients, and correlations between COPD and other previously unevaluated clinical variables.Materials and methods: Lung cancer patients (stages I to IV) diagnosed with NSCLC between January 2008 and December 2015 at six university hospitals were enrolled in the study cohort and retrospectively evaluated. Clinical parameters were compared between spirometrically diagnosed COPD and non-COPD groups. Correlations between COPD status and other variables were evaluated. In order to reduce the effect of potential confounders and selection bias, we performed adjustment for differences in baseline parameters by using propensity score matching (PSM). After PSM, clinical variables were evaluated for their effects on overall survival (OS).Results: Of the 345 patients enrolled in the study, 277 were categorized as non-COPD and 68 as COPD. Old age, male gender, and wild-type EGFR were significantly correlated with COPD. By univariate analysis of 218 patients in a propensity score matched cohort, not receiving active anticancer treatment, advanced stage, and COPD were significantly associated with shorter OS. Multivariate analysis showed that not receiving active anticancer treatment, advanced cancer stage, and COPD (P=0.044, HR: 1.526, 95% CI: 1.012–2.300) were significant predictors of shorter OS.Conclusion: In the present study, never-smoker NSCLC patients with COPD had shorter OS times, compared to non-COPD never-smoker NSCLC patients.Keywords: never smoker, overall survival, risk factor

Ho Cheol Kim,1,* Tae Hoon Kim,2,* Chin Kook Rhee,3 Minkyu Han,4 Yeon-Mok Oh1 1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 4Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea *These authors contributed equally to this work Purpose: Although patients with tuberculous destroyed lung (TDL) receive long-acting muscarinic antagonist (LAMA) inhaler therapy, its effectiveness is not clear. This study evaluated the effect of LAMA inhaler therapy on mortality in patients with TDL and airflow limitation.Patients and methods: A retrospective cohort of 683 patients with TDL and airflow limitation was analyzed in this study. The mortality was compared between 177 patients treated with LAMA inhalers >360 days (LAMA group) and 506 patients not treated with LAMA inhalers or treated with LAMA inhalers for

Yong Il Hwang,1,2 Yong Bum Park,2,3 Hyoung Kyu Yoon,4 Tae-Hyung Kim,5 Kwang Ha Yoo,6 Chin Kook Rhee,4 Joo Hun Park,7 Seung Hun Jang,1,2 Sunghoon Park,1,2 Joo-Hee Kim,1,2 Jiyoung Park,1,2 Ki-Suck Jung1,2 1Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang-si, South Korea; 2Lung Research Institute of Hallym University College of Medicine, Chuncheon, South Korea; 3Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Chuncheon, South Korea; 4Division of Pulmonology, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 5Division of Pulmonology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea; 7Department of Internal Medicine, Ajou University School of Medicine, Suwon, South Korea Background: Smoking is a major risk factor for COPD. However, there is low COPD awareness among smokers. We conducted a field survey to investigate COPD awareness, optimistic bias associated with COPD, and COPD prevalence (using handheld spirometry) among current male smokers. Subjects and methods: We enrolled currently smoking males aged over 40 years, who completed a self-administered questionnaire. The questionnaire consisted of six parts: 1) baseline demographics, 2) participants’ awareness of COPD and pulmonary function tests, 3) presence of COPD-related respiratory symptoms and experience with pulmonary function testing, 4) optimistic bias about COPD, 5) willingness to change attitude toward respiratory health, and 6) preference of media for obtaining health-related information. Pulmonary function was assessed via handheld spirometry by two experienced pulmonary function laboratory technicians after completion of the questionnaire. Results: We enrolled 105 participants. Only 24.8% knew of COPD. Awareness of pulmonary function testing was reported by 41.9% of participants, and 30.5% had previously undertaken pulmonary function tests. Among the subjects who had not previously undergone pulmonary function tests, 47% were not aware of their existence. The mean optimistic bias scores were 3.9 and 4.0, respectively, reflecting the general perception, among participants, that they were about as likely to develop COPD as similarly aged smokers and friends, respectively. A total of 40.0% of participants perceived personal COPD risk to be lower than COPD risk among their friends. Abnormal handheld spirometry results were observed in 28.6% of participants. Among the subjects with abnormal handheld spirometry results, 36.7% had FEV1 values

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases. Keywords: asthma, COPD, ACO, exacerbation, club cell secretory protein-16, smoking

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 (

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P

Hye Sook Choi,1 Ju Ock Na,2 Jong Deog Lee,3 Kyeong-Cheol Shin,4 Chin Kook Rhee,5 Yong Il Hwang,6 Seong Yong Lim,7 Kwang Ha Yoo,8 Ki Suck Jung,6 Yong Bum Park9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyunghee University Hospital, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Pulmonary Medicine, Soonchunhyang University Cheonan Hospital, Cheonan-si, Republic of Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University, Jinju, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea; 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea Background: The 2017 GOLD guidelines revised assessment of COPD by eliminating the FEV1 criterion.Aim: First, we explored the redistribution of 2011 GOLD groups by reference to the 2017 GOLD criteria. Second, we investigated the characteristics of GOLD B patients and the natural course of GOLD B patients according to the 2017 GOLD guidelines.Methods: In total, 2,010 COPD patients in the Korean COPD Subgroup Study cohort were analyzed at baseline and 1 year after enrollment.Results: The 2011 GOLD C patients were redistributed to the 2017 A (64.5%) and C (35.4%) groups. The 2011 GOLD D patients were redistributed to the 2017 B (61.6%) and D (38.6%) groups. The GOLD B patients constituted 62.7% of all patients according to the 2017 classification. Such patients exhibited higher % predicted FEV1 values, longer six-minute walk distances, fewer symptoms, and lower inflammatory marker levels than GOLD D patients. Most GOLD B patients remained in that group (69.1%), but 13.8% progressed to group D at 1-year follow-up. The factors associated with progression from GOLD B to GOLD D were older age, higher modified Medical Research Council (mMRC) and St George’s Respiratory Questionnaire (SGRQ) symptom scores, and a lower % predicted FEV1 value.Conclusion: Severe symptoms, poorer health status, and greater airflow limitation increased patients’ risk of exacerbation and progression from group B to group D when the 2017 GOLD criteria were applied. Keywords: COPD, GOLD B, progression

Yong Suk Jo,1 Yee Hyung Kim,2 Jung Yeon Lee,3 Kyungjoo Kim,4 Ki-Suck Jung,5 Kwang Ha Yoo,6 Chin Kook Rhee4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konkuk University Chungju Hospital, Chungju, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown. We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs. Methods: We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data. COPD was confirmed by spirometry. BMI was used to stratify patients into four categories: underweight (BMI

Jeong Uk Lim, Chang Dong Yeo, Chin Kook Rhee, Yong Hyun Kim, Chan Kwon Park, Ju Sang Kim, Jin Woo Kim, Seung Joon Kim, Hyoung Kyu Yoon, Sang Haak Lee Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Objectives: Focusing on the advanced non-small cell lung cancer (NSCLC) patients without driver mutations can elucidate the clinical impact of COPD on treatment outcomes. The present study evaluated the effects of COPD on the overall survival of driver mutation-negative NSCLC patients undergoing conventional chemotherapy as the first-line treatment. Patients and methods: Medical records of stage IIIB and IV NSCLC patients from January 2008 to December 2015 from six university hospitals were reviewed. Results: The total study population consisted of 197 patients; 92 (46.7%) were COPD patients and 105 (53.3%) were non-COPD patients. The median survival in the non-COPD group was 11.5 months, compared to 9.2 months in the COPD group. Univariate analysis showed that old age (>70 years), high Eastern Cooperative Oncology Group status score (2–3), squamous cell histology, and COPD were risk factors for mortality. The presence of COPD was a significant prognostic factor in univariate analysis (hazard ratio [HR], 1.402; p=0.037), but not in multivariate analysis (HR, 1.275; p=0.144). Subgroup analysis of 143 smokers showed that COPD was a significant prognostic factor on multivariate analysis (HR, 1.726; p=0.006). In 154 stage IV patients, COPD was also a prognostic factor in multivariate analysis (HR, 1.479; p=0.039). Conclusion: COPD had a negative impact on overall survival in the stage IV NSCLC and smoker NSCLC patients who underwent conventional chemotherapy. Keywords: non-small cell lung cancer, chronic obstructive pulmonary disease, smoker, overall survival

Jeong Uk Lim,1 Ji-Hyun Lee,2 Tae-Hyung Kim,3 Jae Seung Lee,4 Sang-Do Lee,4 Yeon-Mok Oh,4 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea; 4Department 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 Introduction: Phenotyping of chronic bronchitis (CB) using COPD assessment tool (CAT) scores and St George’s Respiratory Questionnaire (SGRQ) has rarely been attempted. The present study defined CB using CAT 1 and 2 scores and the questions on the severity of cough and sputum from the SGRQ. Furthermore, the predictability of CT parameters was also assessed for each CB definition. Materials and methods: Patients enrolled in the Korean Obstructive Lung Disease study from June 2005 to October 2015 were evaluated for this study. The patients were spirometrically diagnosed with COPD and had a smoking history of >10 pack-years. Volumetric CT scans were performed for each patient upon enrollment in the cohort. Two definitions of CB using CAT 1/2 scores and SGRQ questions were used to phenotype CB among the study patients. Receiver operating characteristic curve analysis was performed to estimate the predictability of CT parameters for the CB phenotypes. Results: Using CAT 1/2 scores, 57 of 279 (20.4%) patients had CB, and 178 of 573 (31.1%) had CB when the SGRQ questions were used to phenotype it. Total CAT and SGRQ scores were significantly higher in the CB group than those in the non-CB group for both definitions of CB. Forced expiratory volume in 1 second was lower for both CAT-defined and SGRQ-defined CB than that in the non-CB group. Mean wall thickness was significantly higher for both CB groups than in the non-CB group. Expiratory lung volume was higher and mean lung density was significantly lower for the SGRQ-defined CB group than non-CB group. Conclusion: The 2 CB definitions using CAT scores and the SGRQ questions correlated with associated CT airway parameters. SGRQ-defined CB better reflected the accompaniment of small airway obstruction when compared with CAT-defined CB. Keywords: chronic bronchitis, chronic obstructive pulmonary disease, chest CT

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea Purpose: Asthma–COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of L-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.Patients and methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary L-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.Results: Urinary L-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary L-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary L-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid

Seon Cheol Park,1,2 Young Sam Kim,3 Young Ae Kang,3 Eun Cheol Park,4 Cheung Soo Shin,5 Dong Wook Kim,6 Chin Kook Rhee7 1Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang-si, Korea; 2Department of Medicine, Yonsei University College of Medicine, Seoul, Korea; 3Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 4Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea; 5Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea; 6Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang-si, Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Purpose: Previous studies have reported that anemia increased mortality in patients with COPD. However, it is unclear whether anemia is associated with increased COPD mortality in the general population. The purpose of our study is to identify whether anemia is related to long-term mortality in COPD using a large population-based database. Patients and methods: Using the National Health Insurance Service-Health Screening Cohort, we identified COPD patients with available hemoglobin level. We analyzed mortality among patients with COPD from 2003 to 2013 according to hemoglobin level. Results: A total of 7,114 patients with COPD were identified. Mean age was 65.0±9.3 years, and 62.9% were male. Anemia was present in 469 patients (6.6%). The overall mortality rate was 46.5% in anemia and 32.1% in non-anemia groups (p

Min-Hye Kim,1 Chin Kook Rhee,2 Kyungjoo Kim,2 Sang Hyun Kim,3 Jung Yeon Lee,4 Yee Hyung Kim,5 Kwang Ha Yoo,6 Young-Joo Cho,1 Ki-Suck Jung,7 Jin Hwa Lee1 1Department of Internal Medicine, College of Medicine, Ewha Womans University, 2Department of Internal Medicine, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, 3Big Data Division, Health Insurance Review and Assessment Service, Wonju, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konkuk University Chungju Hospital, Chungju, 5Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 6Department of Internal Medicine, Konkuk University College of Medicine, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Background: Asthma and COPD are heterogeneous diseases. Patients with both disease features (asthma–COPD overlap [ACO]) are common. However, clinical characteristics and socio-economic burden of ACO are still controversial. The aim of this study was to identify the heterogeneity of ACO and to find out the subtypes with clinical impact among ACO subtypes. Methods: In the Korean National Health and Nutrition Examination Survey (KNHANES) conducted between 2007 and 2012, subjects who were ≥40 years and had prebronchodilator FEV1/FVC

Kyung Hoon Kim,1 Hye Seon Kang,2 Ju Sang Kim,3 Hyoung Kyu Yoon,4 Sung Kyoung Kim,5 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 3Division of Pulmonary Medicine, Department of Internal Medicine, Incheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 5Division of Pulmonary Medicine, Department of Internal Medicine, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea Introduction: Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.Method: A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea. The study subjects were limited to patients who had taken 500 µg of roflumilast. We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.Results: Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription. Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation. Low–body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, p=0.006; BMI

Jeong Uk Lim,1 Kyungjoo Kim,2 Sang Hyun Kim,3 Myung Goo Lee,4 Sang Yeub Lee,5 Kwang Ha Yoo,6 Sang Haak Lee,1 Ki-Suck Jung,7 Chin Kook Rhee,2 Yong Il Hwang7 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Big Data Division, Health Insurance Review and Assessment Service, Wonju, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, 5Department of Internal Medicine, Korea University, Anam Hospital, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Introduction: Patients with mild to moderate chronic obstructive pulmonary disease (COPD) are underdiagnosed and undertreated due to the asymptomatic nature of the disease. Previous studies on patients with mild COPD have focused on symptomatic patients. Therefore, in this study, we evaluated the treatment status of patients with early COPD in Korea.Materials and methods: We compared hospital visits, medical costs per person, and COPD medication use by patients with COPD screened from the general population and COPD cohort patients. Patients with COPD aged ≥40 years with the value of forced expiratory volume in 1 s (FEV1) ≥60% were selected from the 2007 to 2012 Korea National Health and Nutrition Examination Survey (KNHANES) data. Data including the number of outpatient clinic visits, admission to hospitals, COPD-related medications, and medical costs were obtained from the Health Insurance Review and Assessment Service and were compared with the data of patients with COPD with FEV1 ≥60% from the Korean COPD Subtype Study (KOCOSS) cohort.Results: Based on EuroQol 5-dimension questionnaire index scores of 0.9±0.14, we found that patients with COPD from the KNHANES group showed few symptoms compared to those from the KOCOSS cohort. In 2007, among the patients with COPD with an FEV1 value of ≥60%, only 3.6% from the KNHANES group and 30% from the KOCOSS cohort visited medical facilities. Total medical cost per person per year increased from 264.37±663.41 US Dollars (USD) in 2007 to 797.00±2,724.21 USD in 2012 for the KNHANES group. In 2012, only 20.7% of the patients from KNHANES database received long-acting muscarinic agonists (LAMA), whereas 78.7% of the patients from KOCOSS database received LAMA.Conclusion: Medical resource utilization and medical costs per person for patients with early COPD in Korea increased. However, asymptomatic patients with COPD represented by the KNHANES group do not receive adequate long-term treatment compared to relatively symptomatic patients, and require more clinical attention from physicians. Keywords: early COPD, medical cost, medical utilization

Jeong Uk Lim,1 Jae Ha Lee,2 Ju Sang Kim,3 Yong Il Hwang,4 Tae-Hyung Kim,5 Seong Yong Lim,6 Kwang Ha Yoo,7 Ki-Suck Jung,4 Young Kyoon Kim,8 Chin Kook Rhee8 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, 2Division of Pulmonology, Department of Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, 3Division of Pulmonary Medicine, Department of Internal Medicine, Incheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, 5Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Introduction: A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD. The Asia-Pacific classification of BMI has a lower cutoff for overweight and obese categories compared to the World Health Organization (WHO) classification. The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific. Patients and methods: Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation. We enrolled 1,462 patients. Medical history including age, sex, St George’s Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV1) were evaluated. Patients were categorized into different BMI groups according to the two BMI classification systems. Result: FEV1 and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse “U”-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied. When Asia-Pacific cutoffs were applied, FEV1 and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria. From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications. The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems. Conclusion: The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms. Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification. Keywords: body mass index, COPD, comorbidity

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

Chin Kook Rhee,1 Kyungjoo Kim,1 Hyoung Kyu Yoon,2 Jee-Ae Kim,3 Sang Hyun Kim,4 Sang Haak Lee,5 Yong Bum Park,6 Ki-Suck Jung,7 Kwang Ha Yoo,8 Yong Il Hwang7 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Pharmaceutical Policy Evaluation Research Team, Research Institution, 4Big Data Division, Health Insurance Review and Assessment Service, Wonju, 5Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, 6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. Methods: Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. Results: A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV1) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV1 (%), and lower EQ-5D score were significantly associated with medical costs. Conclusion: Even in early COPD patients, some of them eventually progressed and utilized health care for COPD. Keywords: early COPD, KNHANES, NHI, HIRA, utilization, cost

Hyonsoo Joo,1 Deokjae Han,1 Jae Ha Lee,2 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonology, Department of Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea Abstract: Many patients suffering from asthma or COPD have overlapping features of both diseases. However, a phenotypical approach for evaluating asthma–COPD overlap syndrome (ACOS) has not been established. In this report, we examined the phenotypes in patients with ACOS. Patients diagnosed with ACOS between 2011 and 2015 were identified and ­classified into four phenotype groups. Group A was composed of patients who smoked

Sei Won Kim,1,* Chin Kook Rhee,2,* Ki Uk Kim,3 Sang Haak Lee,4 Hun Gyu Hwang,5 Yu Il Kim,6 Deog Kyeom Kim,7 Sang Do Lee,8 Yeon-Mok Oh,8 Hyoung Kyu Yoon1 On behalf of the KOLD Study Group 1Division of Pulmonary, Department of Internal Medicine, Yeouido St Mary’s Hospital, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Internal Medicine, Pusan National University, School of Medicine, Busan, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 5Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi, 6Division of Pulmonology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 8Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work Background: Interleukin (IL)-33 promotes T helper (Th)2 immunity and systemic inflammation. The role of IL-33 in asthma has been widely investigated. IL-33 has also been suggested to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the clinical significance and usefulness of plasma IL-33 level in patients with COPD. Methods: A total of 307 patients with stable COPD from 15 centers, who were in the Korean Obstructive Lung Disease cohort, were enrolled in this study. Plasma IL-33 levels were measured by enzyme-linked immunosorbent assay. We analyzed the association between IL-33 level and other clinical characteristics related to COPD. We also examined the features of patients with COPD who exhibited high IL-33 levels. Results: IL-33 levels varied, but were very low in most patients. Eosinophil count was significantly correlated with a plasma IL-33 level. In addition, old age and current smoking were related to a low IL-33 level. Significantly more patients with a higher IL-33 level had chronic bronchitis compared with those with a low IL-33 level. Conclusion: Plasma IL-33 level in patients with stable COPD was related to eosinophil count and chronic bronchitis phenotype. Further studies are needed to identify the precise mechanisms of IL-33/ST2 pathway in patients with COPD. Keywords: biomarker, cytokine, interleukin-33, eosinophil, pathogenesis, chronic bronchitis

Jongmin Lee,1 Jae Ha Lee,1 Jee-Ae Kim,2 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, Wonju-si, Republic of Korea Background: There are only a few longitudinal studies regarding medical utilization and costs for patients with COPD. The purpose of this study was to analyze the trend of medical utilization and costs on a long-term basis. Methods: Using the Korean Health Insurance Review and Assessment Service (HIRA) data from 2008 to 2013, COPD patients were identified. The trend of medical utilization and costs was also analyzed. Results: The number of COPD patients increased by 13.9% from 2008 to 2013. During the same period, the cost of COPD medication increased by 78.2%. Methylxanthine and systemic beta agonists were most widely prescribed between 2008 and 2013. However, inhaled medications such as long-acting beta-2 agonist (LABA), long-acting muscarinic agonist, and inhaled corticosteroid plus LABA were dispensed to a relatively low proportion of patients with COPD. The number of patients who were prescribed inhaled medications increased gradually from 2008 to 2013, while the number of patients prescribed systemic beta agonist and methylxanthine has decreased since 2010. Conclusion: This study shows that there is a large gap between the COPD guidelines and clinical practice in Korea. Training programs for primary care physicians on diagnosis and guideline-based treatment are needed to improve the management of COPD. Keywords: pulmonary disease, chronic obstructive, drug prescriptions, medical utilization, medical cost

Suh-Young Lee,1,* Hye Yun Park,2,* Eun Kyung Kim,3 Seong Yong Lim,4 Chin Kook Rhee,5 Yong Il Hwang,6 Yeon-Mok Oh,7 Sang Do Lee,7 Yong Bum Park1 On behalf of the KOLD Study Group 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 3Department of Internal Medicine, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, 4Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 5Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Gyeonggido, 7Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea *These authors contributed equally to this work Background: The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2-agonist (LABA) treatment in patients with asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) compared to patients with COPD alone has rarely been examined. This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients. Methods: Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. Subjects began a 3-month ICS/LABA treatment after a washout period. ACOS was defined when the patients had 1) a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey and 2) a positive bronchodilator response. Results: Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for ACOS. After a 3-month treatment with ICS/LABA, the increase in forced expiratory volume in 1 second (FEV1) was significantly greater in ACOS patients than in those with COPD alone (240.2±33.5 vs 124.6±19.8 mL, P=0.002). This increase in FEV1 persisted even after adjustment for confounding factors (adjusted P=0.002). According to severity of baseline FEV1, the ACOS group showed a significantly greater increase in FEV1 than the COPD-alone group in patients with mild-to-moderate airflow limitation (223.2±42.9 vs 84.6±25.3 mL, P=0.005), whereas there was no statistically significant difference in patients with severe to very severe airflow limitation. Conclusion: This study provides clinical evidence that ACOS patients with mild-to-moderate airflow limitation showed a greater response in lung function after 3 months of ICS/LABA combination treatment. Keywords: pulmonary disease, chronic obstructive, asthma, respiratory function tests

Hye Seon Kang, Chin Kook Rhee, Sung Kyoung Kim, Jin Woo Kim, Sang Haak Lee, Hyung Kyu Yoon, Joong Hyun Ahn, Yong Hyun Kim Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Purpose: We compared the clinical characteristics and treatment outcomes of patients with eosinophilic and neutrophilic COPD exacerbations requiring hospital admission. Patients and methods: This was a retrospective multicenter study performed between January 2010 and December 2014. In all, 1,688 COPD patients admitted via the outpatient clinics or emergency departments of six university hospitals were enrolled. The patients were grouped by complete blood counts: eosinophilic group, >2% peripheral blood eosinophils, and neutrophilic group, >65% peripheral blood neutrophils or >11,000 leukocytes/mL. The patients with radiographic evidence of pneumonia at the time of admission, those with lung cancer, those admitted for treatment of other medical problems, and those who chronically used steroids were excluded. Results: A total of 605 patients hospitalized with COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included. Pulmonary functions, including the forced expiratory volume in 1 second and forced vital capacity, were better in patients with eosinophilic exacerbations. Treatment outcomes, including the rate of admission to the intensive care unit and mortality, were poorer in patients with neutrophilic exacerbations (4.5% vs 12.4%, P=0.004; 1.1% vs 4.5%, P=0.043, respectively). Congestive heart failure (odds ratio [OR] =3.40, 95% confidence interval [CI]: 1.28–9.01) and neutrophilic exacerbation (OR =2.81, 95% CI: 1.21–6.52) were independent risk factors for intensive care unit admission. Conclusion: COPD patients with neutrophilic exacerbations experienced worse clinical outcomes than did those with eosinophilic exacerbations. The peripheral blood eosinophil count may be a useful predictor of clinical progress during hospitalization of COPD patients with acute exacerbations. Keywords: eosinophilia, neutrophilia, pulmonary disease, chronic obstructive, exacerbations, intensive care unit

Joon Young Choi,1 Hyoung Kyu Yoon,2 Seoung Ju Park,3 Yong Bum Park,4 Kyeong-Cheol Shin,5 Ju Ock Na,6 Kwang Ha Yoo,7 Ki-Suck Jung,8 Young Kyoon Kim,1 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 5Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Background: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups.Methods: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups.Results: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups.Conclusion: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups. Keywords: chronic obstructive pulmonary disease, chronic bronchitis, COPD assess­ment test

Hyun Lee,1 Chin Kook Rhee,2 Byung-Jae Lee,3 Dong-Chull Choi,3 Jee-Ae Kim,4 Sang Hyun Kim,5 Yoolwon Jeong,6 Tae-Hyung Kim,7 Gyu Rak Chon,8 Ki-Suck Jung,9 Sang Haak Lee,10 David Price,11 Kwang Ha Yoo,12,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 4Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 5Big Data Division, Health Insurance Review and Assessment Service, Seoul, 6Division of Chronic Disease Control, Korea Centers for Disease Control and Prevention, Osong, 7Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, 8Department of Pulmonary and Critical Care Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju City, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 10Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 11Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 12Division of Pulmonary, Allergy and Critical Care Medicine Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Backround: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P

Sei Won Kim,1 Kyungdo Han,2 Shin Young Kim,3 Chan Kwon Park,3 Chin Kook Rhee,1 Hyoung Kyu Yoon3 1Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 3Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Potential associations between oral health and respiratory disease, including chronic obstructive pulmonary disease (COPD), have been suggested in several studies. Among the indicators reflecting oral health, the number of natural teeth is an integrated and simple index to assess in the clinic. In this study, we examined the relationship between the number of natural teeth and airflow obstruction, which is a central feature of COPD.Methods: A total of 3,089 participants over 40 years, who underwent reliable spirometry and oral health assessments were selected from the Korean National Health and Nutrition Examination Survey 2012, a cross-sectional and nationally representative survey. Spirometry results were classified as normal, restrictive, or obstructive pattern. Total number and pairs of natural teeth were counted after excluding third molars.Results: After adjusting for other variables, such as age, body mass index, socioeconomic factors, and oral health factors, the group with airflow obstruction showed significantly fewer natural teeth than the other groups in males (P=0.014 and 0.008 for total number and total pairs of natural teeth, respectively). Compared with participants with full dentition, the adjusted odds ratio for airflow obstruction in males with fewer than 20 natural teeth was 4.18 (95% confidence interval: 2.06–8.49) and with fewer than 10 pairs of natural teeth was 4.74 (95% confidence interval: 2.34–9.62). However, there was no significant association between the total number or pairs of natural teeth and airflow obstruction after adjustment in females.Conclusions: Loss of natural teeth was significantly associated with the presence of airflow obstruction in males. Our finding suggests that the number of natural teeth could be one of the available indices for obstructive lung diseases, including COPD. Keywords: tooth loss, oral health, airflow obstruction, chronic obstructive pulmonary disease

Chin Kook Rhee,1 Jung Hyun Chang,2 Eu gene Choi,3 Hyun kuk Kim,4 Yong-Soo Kwon,5 Sun Young Kyung,6 Ji-Hyun Lee,7 Myung Jae Park,8 Kwang Ha Yoo,9 Yeon Mok Oh10 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Ewha Womans University Medical Center, Seoul, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Daejeon Hankook Hospital, Daejeon, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, CHA Bundang Medical Center of CHA University, Seongnam, 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, KyungHee University Hospital, Seoul, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, 10Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Abstract: A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals. Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, –7.7%–8.6%). Intention-to-treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, –0.2%; 95% confidence interval, –9.0%–8.8%), respectively. These results confirm that zabofloxacin is not inferior to moxifloxacin. The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22). Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group. Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97). The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12). Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. Keywords: chronic obstructive pulmonary disease, exacerbation, zabofloxacin, quinolone, EXACT-PRO, CAT

Sei Won Kim,1 Jong Min Lee,1 Jick Hwan Ha,1 Hyeon Hui Kang,1 Chin Kook Rhee,1 Jin Woo Kim,1 Hwa Sik Moon,1 Ki Hyun Baek,2 Sang Haak Lee1 1Division of Pulmonology, Critical Care and Sleep Medicine, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Background: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. Patients and methods: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. Results: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20–6.48, P=0.018) compared with carriers in the dominant model. Conclusion: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD. Keywords: chronic obstructive pulmonary disease, osteoporosis, vitamin D receptor gene, polymorphism, haplotype

Chin Kook Rhee,1 Jin Woo Kim,2 Yong Il Hwang,3 Jin Hwa Lee,4 Ki-Suck Jung,3 Myung Goo Lee,5 Kwang Ha Yoo,6 Sang Haak Lee,7 Kyeong-Cheol Shin,8 Hyoung Kyu Yoon9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 8Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 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. Keywords: COPD, CAT, mMRC, concordance, discrepancy

JinHee Kim,1 Chin Kook Rhee,2 Kwang Ha Yoo,3 Young Sam Kim,4 Sei Won Lee,5 Yong Bum Park,6 Jin Hwa Lee,7 YeonMok Oh,5 Sang Do Lee,5 Yuri Kim,8 KyungJoo Kim,8 HyoungKyu Yoon9 1Office of Health Service Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea; 2Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, Korea; 3Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 4Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 5Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 7Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea; 8Department of Clinical Research Support, National Strategic Coordinating Center for Clinical Research, Seoul, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, Korea Background: Patients with high grade chronic pulmonary obstructive disease (COPD) account for much of the COPD-related mortality and incur excessive financial burdens and medical care utilization. We aimed to determine the characteristics and medical care use of such patients using nationwide data from the Korean Health Insurance Review and Assessment Service in 2009. Materials and methods: Patients with COPD were identified by searching with the International Classification of Diseases–10th Revision for those using medication. Patients with high grade COPD were selected based on their patterns of tertiary institute visits and medication use. Results: The numbers of patients with high grade COPD increased rapidly in Korea during the study period, and they showed a high prevalence of comorbid disease. The total medical costs were over three times higher in patients with high grade COPD compared with those without it ($3,744 versus $1,183; P < 0.001). Medication costs comprised the largest portion of medical cost, but most impact came from hospitalization and exacerbation in both groups of patients. COPD grade and hospitalization in the previous year were the major factors affecting medical costs and days of utilizing health care resources. Conclusion: Patients with high grade COPD impose a high economic burden on the health care system in Korea. Prevention of progression to high grade COPD is important, both clinically and economically. Keywords: COPD, population characteristics, health care utilization, medical cost

Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8–12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma, airway remodeling, muscarinic receptor

Kang HS, Rhee CK, Kim SK, Kim JW, Lee SH, Yoon HK, Ahn JH, Kim YH. Int J Chron Obstruct Pulmon Dis. 2016;11:2467–2473.Page 2467, Abstract, Results section, line 1, the text “COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included” should read “COPD exacerbations (177 eosinophilic, 380 neutrophilic and 48 paucigranulocytic) were included. Of these, we compared patients with eosinophilic and neutrophilic COPD exacerbations”.Read the original article