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Hye-Rin Kang,1,* So Jeong Kim,2,* Ju Gang Nam,3 Young Sik Park,4 Chang-Hoon Lee4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Veteran Health Service Medical Center, Seoul, 05368, Republic of Korea; 2Division of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Gyeonggi-do, 18450, Republic of Korea; 3Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Hoon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-4743, Fax +82-2-762-9662, Email kauri670@empal.comIntroduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality.Methods: The study included participants aged ≥ 40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality.Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23– 2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20– 3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98– 1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85– 3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15– 4.40).Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.Keywords: pulmonary disease, chronic obstructive, smokers, nonsmokers, cigarette smoking, comorbidity

Jong Geol Jang,* Young Seok Lee,* Kyung Soo Hong, June Hong Ahn Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Jong Geol Jang; June Hong Ahn, Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu, 42415, Republic of Korea, Tel +82-53-620-4367 ; +82-53-640-6577, Email jang83@ynu.ac.kr; fireajh@gmail.comPurpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD.Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants’ handling of the device by using a check list.Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse.Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.Keywords: chronic obstructive pulmonary disease, bronchodilators, misuse, soft mist inhaler

Li-Ting Kao,1 Shian-Chin Ko,2 Ping-Jen Chen,3,4 Yu-Cih Wu,5 Kuang-Ming Liao,6 Yi-Shan Liang,1 Chung-Han Ho,5,7,8 Fu-Wen Liang9– 11 1Department of Respiratory Therapy, Chi Mei Medical Center, Tainan, Taiwan; 2Center for Palliative Care, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Family Medicine and Division of Geriatrics and Gerontology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; 6Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan City, Taiwan; 8Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 9Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chung-Han Ho, Department of Medical Research, Chi Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan City, 71004, Taiwan, Tel +886-6-281-2811, Email ho.c.hank@gmail.com Fu-Wen Liang, Department of Public Health, College of Health Sciences, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung, 807, Taiwan, Tel +886-7-312-1101 Ext 2786, Fax +886-7-311-0811, Email fwliang@kmu.edu.twPurpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD.Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan’s National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization.Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions—especially cancer—and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1– 2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1– 2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years.Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.Keywords: cancer comorbidity, inpatient care, joinpoint regression, Taiwan’s health insurance database

Yan Shen Kee,1 Chee Kuan Wong,1 Muhammad Anis Abdul Aziz,1 Mohd Idzwan Zakaria,2 Fatimah Mohd Shaarif,2 Kee Seong Ng,1 Chong Kin Liam,1 Yong Kek Pang,1 Ee Ming Khoo3 1Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Academic Unit Trauma and Emergency, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaCorrespondence: Chee Kuan Wong, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia, Tel +60178712807, Email cheekuanwong76@gmail.comPurpose: Readmission of chronic obstructive pulmonary disease (COPD) has been used as a measure of performance for COPD care. This study aimed to determine the rate of readmission of COPD in tertiary care hospital in Malaysia and its associated factors.Patients and Methods: A retrospective cohort study was conducted at a tertiary care hospital in Malaysia from 1st January to 21st May 2019. Seventy admissions for COPD exacerbation involving 58 patients were analyzed.Results: The majority of the patients were male (89.8%), had a mean age of 71.95 ± 7.24 years and a median smoking history of 40 (IQR = 25) pack-years, 84.5% were in GOLD group D and 91.4% had a mMRC grading of 2 or greater. Approximately 60.3% had upper or lower respiratory tract infection as the cause of exacerbation; one in five patients had uncompensated hypercapnic respiratory failure at presentation, and 27.6% needed mechanical ventilatory support. Approximately 43.1% of patients had a history of exacerbation that required hospitalisation in the past year. The mean blood eosinophil concentration was 0.38 ± 0.46 x109 cells/L. The 30-day readmission rate was 20.3%, revisit rate to the emergency room within 30 days after discharge was 3.4%, and in-hospital mortality rate was 1.7%. Among all characteristics, a higher baseline mMRC grade (p = 0.038) and history of exacerbation in the past 1 year (p < 0.001) were statistically associated with 30-day readmission.Conclusion: The 30-day readmission rate for COPD exacerbation in a Malaysian tertiary hospital is similar to the rates in high-income countries. Exacerbation in the previous year and a higher baseline mMRC grading were significant risk factors for 30-day readmission in patients with COPD. Strategies of COPD management should concentrate on improvement of symptoms control by optimisation of pharmacotherapy, and early initiation of pulmonary rehabilitation, and structured integrated care programs to reduce readmission rates.Keywords: COPD, exacerbation, readmission, baseline mMRC, nurse educator

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

Hyewon Seo,1 Yun Su Sim,2 Kyung Hoon Min,3 Jae Ha Lee,4 Byung-Keun Kim,5 Yeon Mok Oh,6 Seung Won Ra,7 Tae-Hyung Kim,8 Yong Il Hwang,9 Jeong-Woong Park10 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, 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 Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 6Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 9Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 10Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Incheon, Republic of KoreaCorrespondence: Jeong-Woong Park, Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Namdong-daero 774 beon-gil, Namdong, Incheon, 21565, Republic of Korea, Tel +82-10-5574-0164, Fax +82-32-469-4320, Email jwpark@gilhospital.comPurpose: Data regarding the relationship between microbiologic features and comorbidities in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are limited. The aim of this study was to correlate microbiologic findings with comorbidities in patients with moderate to severe AECOPD.Patients and Methods: This multicenter observational study included patients with AECOPD seen at 28 hospitals in South Korea between January 2015 and December 2018, and the data were retrospectively collected. Pathogens were examined in patients with either pulmonary or extrapulmonary comorbidities, and compared to those of patients without comorbidities. The relationship between pathogen type and the number of comorbidities was also evaluated.Results: Bacterial infections (178 [37.2%] vs 203 [28.7%], p = 0.002) and co-infections with bacteria and viruses (65 [13.6%] vs 57 [8.1%], p = 0.002) were more prevalent in patients with pulmonary comorbidities. Bacterial pathogens (280 [34.7%] vs 101 [26.7%], p=0.006) were detected at a higher rate in patients with extrapulmonary comorbidities. Previous pulmonary tuberculosis (PTB), bronchiectasis, and diabetes mellitus were risk factors for bacterial infection, and congestive heart failure was a risk factor for bacterial and viral co-infection. As the number of comorbidities increased, the risk of bacterial infection increased considerably. Pseudomonas aeruginosa was more frequently identified in patients with previous PTB (57 [15.3%] vs 59 [7.4%], p < 0.001) and bronchiectasis (33 [19.6%] vs 83 [8.3%], p < 0.001).Conclusion: AECOPD patients with comorbidities were more likely to experience infection-related exacerbations compared to those without comorbidities. As the overall number of comorbidities increased, the risk of bacterial infection increased significantly.Keywords: chronic obstructive pulmonary disease, acute exacerbation, comorbidity, bacteria, virus

Jaber S Alqahtani,1,2 Yousef S Aldabayan,3 Abdulelah M Aldhahir,4 Ahmad M Al Rajeh,3 Swapna Mandal,1,5,&ast; John R Hurst1,5,&ast; 1UCL Respiratory, University College London, London, UK; 2Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia; 3Respiratory Care Department, College of Applied Medical Sciences, King Faisal University, Al-Hasa, Saudi Arabia; 4Respiratory Care Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 5Respiratory Medicine, Royal Free London NHS Foundation Trust, London, UK&ast;These authors contributed equally to this workCorrespondence: Jaber S AlqahtaniUCL Respiratory, University College London, Rowland Hill Street, London, NW3 2PF, UKEmail Alqahtani-Jaber@hotmail.comBackground: Readmission following COPD exacerbation is a common and challenging clinical problem. New approaches to predicting readmissions are required to help mitigate risk and develop novel interventions.Methods: We conducted a prospective cohort study in 82 COPD patients admitted due to an exacerbation of COPD. Lung function measures [spirometry, forced oscillation technique (FOT) indices and peak inspiratory flow rate (PIFR)], inflammatory biomarkers and patient-reported outcomes including previous exacerbation history, breathlessness, quality of life and frailty were measured at admission and discharge. We prospectively followed patients for 30 and 90 days to identify predictors for readmission.Results: The readmission rate within 30 days was 38%, and 56% within 90 days. Previous exacerbations, higher COPD Assessment Test score at discharge, frailty, reduced PIFR and increased length of stay were significantly associated with 30-day readmission. PIFR at discharge and frailty had the highest predictive ability for 30-day readmission using area under receiver operating characteristic curves (AUC 0.86, 95% CI 0.78– 0.95, p < 0.001 and AUC 0.81, 95% CI 0.71– 0.90, p < 0.001, respectively). Ninety-day readmissions were significantly associated with previous exacerbations and hospitalisations, higher CAT score at discharge, frailty, depression, lower PIFR and greater expiratory flow limitation (EFL) in the supine position. The best predictive variable in multivariable analysis for both 30- and 90-day readmission was PIFR at discharge.Conclusion: PIFR, CAT score, frailty, and EFL were found to be associated with 30- and 90-day readmission following COPD exacerbation. These findings help identify those at highest risk and to optimise care prior to discharge.Keywords: COPD, exacerbation, admission, readmission, predictor, risk factor, PIFR, frailty, EFL

Chi Young Kim,1,2 Beong Ki Kim,1 Yu Jin Kim,1 Seung Heon Lee,1 Young Sam Kim,3 Je Hyeong Kim1 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea; 2Yonsei University College of Medicine, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Je Hyeong KimDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, 123, Jeogguem-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, Republic of KoreaTel +82-31-412-5950Fax +82-31-413-5950, Email chepraxis@korea.ac.krBackground: Socioeconomic status (SES) is a strong determinant in the development of various diseases. We evaluated the relationship between SES and the incidence of chronic obstructive pulmonary disease (COPD) by using a community-based cohort data.Patients and Methods: Four-year follow-up data of 6341 adults (aged ≥ 40 years), who underwent serial pulmonary function test were analyzed. Incidence of COPD in the participants was defined as the absence of airflow obstruction compatible with COPD (pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio of < 0.7) at baseline but documentation of airflow obstruction in serial testing. SES of patients was divided into quartiles according to household income and educational level. Multivariate logistic regression analyses were performed to estimate the association between SES and COPD incidence.Results: A total of 280 (4.4%) patients developed COPD during the follow-up. The proportion of subjects with lowest education (elementary school) and lowest household income levels (1st quartile) was significantly higher in the COPD group than in the non-COPD group (37.9% vs 29.5%, p< 0.011 and 48.4% vs 30.8%, p< 0.001, respectively). Logistic regression analysis revealed that education level of elementary school was independently associated with COPD incidence after adjustment for sex, age, body mass index, white blood cell count, residence area, and occupation (odds ratio 1.879, 95% confidence interval 1.124– 3.141, p=0.016).Conclusion: In the general population, educational level of elementary school was an independent risk factor for COPD among the components comprising SES. Our results indicate that the implementation of preventive strategies for COPD in those with low educational status could be beneficial.Keywords: chronic obstructive pulmonary disease, socioeconomic status, education level, incidence, prevalence

Yi-Fen Lei,1,2 Hsiu-Chen Lin,3,4 Hsiu-Li Lin,5 Yow-Sheng Uang,2 Hui-Wen Cheng,2 Li-Hsuan Wang2,6 1Department of Pharmacy, Mackay Memorial Hospital, Taipei 10449, Taiwan; 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; 3Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; 4Department of Clinical Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan; 5Department of Neurology, General Cathay Hospital, New Taipei City 22174, Taiwan; 6Department of Pharmacy, Taipei Medical University Hospital, Taipei 11031, TaiwanCorrespondence: Li-Hsuan WangSchool of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 11031, TaiwanEmail shiuan@tmu.edu.twObjective: The effect of statins and fibrates on the risk of chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the effects of statins and fibrates on the risk of COPD in patients with hyperlipidemia.Patients and Methods: This study involved a retrospective cohort with a follow-up period of 6 years. We identified patients who were diagnosed as having hyperlipidemia between 2000 and 2016 from Taiwan’s National Health Insurance Research Database. A Cox proportional hazard model was used to estimate the risk of COPD among different groups. The dose-related effects of statins and fibrates on the risk of COPD were evaluated according to the defined daily dose (DDD).Results: Patients with hyperlipidemia not using statins and fibrates (group II) had a significantly higher risk of COPD compared with their comparison group, with an adjusted hazard ratio (HR) of 1.091 [95% confidence interval (CI): 1.034– 1.152, p < 0.01]. Dose-dependent reduction in the risk of COPD was observed in patients with hyperlipidemia using statins or fibrates compared with patients not using them. Moreover, with an increase in cumulative exposure, a reduced risk of COPD was observed in patients using more than 361 DDDs, with an adjusted HR of 0.474 (95% CI: 0.401– 0.559, p < 0.001). Patients on fibrate monotherapy using more than 541 DDDs were observed to have an adjusted HR of 0.454 (95% CI: 0.226– 0.910, p < 0.05) and those on statin monotherapy with over 361 DDDs were noted to have an adjusted HR of 0.583 (95% CI: 0.459– 0.740, p < 0.001).Conclusion: This study demonstrated that an increase in the cumulative exposure of statins and fibrates significantly reduced the risk of COPD in patients with hyperlipidemia, and the risk reduction appeared to be significantly dose dependent.Keywords: hyperlipidemia, statin, fibrates, chronic obstructive pulmonary disease, cohort study

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

Sang Hee Lee,1,2 Haejung Lee,3 Yun Seong Kim,4 Hye-Kyung Park,5,6 Min Ki Lee,5,6 Ki Uk Kim5,6 1Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo-si, Republic of Korea; 2Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Republic of Korea; 3Department of Nursing, Pusan National University College of Nursing, Yangsan-si, Republic of Korea; 4Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan-si, Republic of Korea; 5Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea; 6Medical Research Institute, Pusan National University Hospital, Busan, Republic of KoreaCorrespondence: Ki Uk KimDepartment of Internal Medicine, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, Republic of KoreaTel +82-51-240-7804Fax +82-51-254-3127Email uk303@naver.comBackground: Disease-specific knowledge is associated with outcomes of patients, but the knowledge level of chronic obstructive pulmonary disease (COPD) patients is known to be low.Objective: We measured the level of disease-specific knowledge and defined factors associated with poor disease knowledge in COPD patients.Materials and Methods: A cross-sectional survey was performed in five hospitals in South Korea. At enrolment, all patients completed the Bristol COPD Knowledge Questionnaire (BCKQ), Satisfaction with Life Scale (SWLS), Personal Resource Questionnaire (PRQ), St. George’s Respiratory Questionnaire (SGRQ), 36-item Short-Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS). The data were analyzed via linear regression to identify factors associated with low-level knowledge of COPD.Results: A total of 245 COPD patients were enrolled in this study. The mean total BCKQ score was 28.1 (SD, 7.4). The lowest scores were seen for items exploring knowledge of “Oral steroids” and “Inhaled steroids”. In univariate analysis, higher level of education (r = 0.17), low income (r = 0.13), the post-bronchodilator FEV1, % predicted (r = − 0.24), the post-bronchodilator FEV1/FVC ratio (r = − 0.13), SWLS (r = 0.15), PRQ (r = 0.16), SF-36 MCS (r = 0.13), HADS-A (r = − 0.17), and HADS-D (r = − 0.28) scores correlated with the BCKQ score (all p < 0.05). FEV1 (r = − 0.25, p < 0.001) and HADS-D score (r = − 0.29, p < 0.001) were significantly associated with the total BCKQ score in multivariate analysis.Conclusion: Our Korean patients with COPD lacked knowledge on oral and inhaled steroid treatments. In particular, patients with higher-level lung function and/or depressive symptoms exhibited poorer disease-specific knowledge; such patients may require additional education.Keywords: chronic obstructive pulmonary disease, disease knowledge, lung function, depression

Seung Hyun Yong,1 Ah Young Leem,1 Young Sam Kim,1 Moo Suk Park,1 Joon Chang,1 Seung Up Kim,2,3 Ji Ye Jung1 1Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Yonsei Liver Center, Severance Hospital, Seoul, Republic of KoreaCorrespondence: Seung Up KimDepartment of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of KoreaEmail ksukorea@yuhs.acJi Ye JungDivision of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaEmail stopyes@yuhs.acBackground: Various comorbidities influence the prognosis of patients with chronic obstructive pulmonary disease (COPD). We investigated if liver fibrosis assessed using fibrosis-4 index (FIB-4) is associated with all-cause mortality in patients with COPD.Methods: We included 756 patients diagnosed with COPD between 2006 and 2010. Medical records were retrospectively reviewed until 2018. FIB-4 was calculated using the following equation: [age (years) × aspartate aminotransferase (IU/L)/(platelet count (109/L) × √alanine aminotransferase (IU/L))].Results: From a total of 756 patients, 582 (76.9%) patients were categorized into survivor and 174 (23.1%) into non-survivor groups. The non-survivor group was significantly older with a higher proportion of male, smoker and lower FEV1/FVC ratio than the survivor group (all P< 0.05). Various comorbidities were more frequently observed in the non-survivor group (P< 0.05). In addition, the non-survivor group had significantly higher FIB-4 than the survivor group (1.8 vs 1.4, P< 0.001). In multivariate analysis, older age (hazard ratio [HR]=1.05), underlying malignancy (HR=2.94), coronary artery occlusive disease (HR=1.58), higher FIB-4 (HR=1.15), and higher GOLD stage (HR=1.26) were significantly associated with the increased risk of all-cause mortality (P< 0.05), whereas body mass index (HR=0.95) was independently protective for all-cause mortality (all P< 0.05). The high FIB-4 (> 1.57) group showed a significantly lower cumulative survival rate than the low FIB-4 (≤ 1.05) group (P=0.031, Log-rank test). In multivariate regression analysis, higher FIB-4 independently predicted the risk of acute exacerbation (odds ratio=1.08, P=0.034).Conclusion: Higher fibrotic burden assessed using FIB-4 was independently predictive of the increased risk of all-cause mortality and acute exacerbation in patients with COPD.Keywords: chronic obstructive pulmonary disease, exacerbation, FIB-4, liver fibrosis, mortality

Ahmed M Alrajeh,1,2 Yousef S Aldabayan,1,2 Abdulelah M Aldhair,1,3 Elisha Pickett,1 Shumonta A Quaderi,1 Jaber S Alqahtani,1,4 Marc Lipman,1 John R Hurst11UCL Respiratory, University College London, London, UK; 2Department of Respiratory Care, King Faisal University, Al Ahsa, Saudi Arabia; 3Department of Respiratory Care, Jazan University, Jazan, Saudi Arabia; 4Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dhahran, Saudi ArabiaIntroduction: Advances in technology offer various solutions that might help optimize the care provided to patients living with chronic non-communicable diseases such as chronic obstructive pulmonary disease (COPD). However, the efficacy of tele-health in COPD is still controversial. Despite this, there appears to be widespread adoption of this technology.Aim: To explore the international use of tele-heath for COPD, to assess the perceptions of clinicians employing tele-health in COPD, and to summarize the techniques that have been used by health care providers to personalize alarm limits for patients with COPD enrolled on tele-health programs.Methods: A cross-sectional survey consisting of 15 questions was distributed and advertised to health care professionals worldwide. Questions were designed to cover five different aspects of tele-health in COPD: purpose of use, equipment type, clinician perceptions, variables monitored, and personalization of alarm limits.Results: A total of 138 participants completed the survey from 29 different countries. As high as 59% of the participants had ever used tele-health for COPD, and 33% still provided tele-health services to patients with COPD. Tele-health was most commonly used for baseline monitoring, with 90% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate, and the use of rescue medication.Conclusion: Twenty-nine different countries use tele-health for managing COPD and therefore there is widespread international use of tele-health in COPD. The majority of providers thought tele-health was effective despite evidence to the contrary.Keywords: chronic obstructive pulmonary disease, COPD, tele-health, home monitoring, alarm limits, perception

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon MinDivision of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaIntroduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107–2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081–3.984; P=0.028] were higher in the group with eosinophil count less than 2%.Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.Keywords: chronic obstructive pulmonary disease, acute exacerbation, bacterial infection, eosinophil

Yong Suk Jo,1 Sung Kyoung Kim,2 Seoung Ju Park,3 Soo-Jung Um,4 Yong-Bum Park,5 Ki Suck Jung,6 Deog Kyeom Kim,7 Kwang Ha Yoo8 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Division of Pulmonology, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; 4Department of Internal Medicine, Division of Pulmonology, Dong-A University Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 6Department of Internal Medicine, Division of Pulmonary Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 7Department of Internal Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 8Department of Internal Medicine, Division of Pulmonary and Allergy Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: FEV1 is the gold standard for assessment of COPD. We compared efficacy of FEV1, inspiratory capacity (IC), and IC to total lung capacity (TLC) ratio in the evaluation of COPD and their association with exacerbation.Methods: We analyzed the association of dyspnea severity, quality of life status, and lung function with lung function measurements and exacerbation risk in 982 patients enrolled in the Korea COPD Subgroup Registry and Subtype Research study. Exacerbation and longitudinal lung function change were evaluated in 3 years’ follow-up.Results: The FEV1, IC, and IC to TLC ratio showed comparable negative correlations with dyspnea severity and quality of life status, and positive correlation with exercise capacity. In patients with >2 events/year, annual rate of change in FEV1 and IC tended to decline more rapidly in those with FEV1 50% (-14.46±19.40 mL/year vs 12.29±9.24 mL/year, P=0.213; -4.75±17.28 mL/year vs -78.05±34.16 mL/year, P=0.056 for FEV1 and IC, respectively), without significance.Conclusion: Longitudinal changes in IC and FEV1 were not significantly associated with exacerbation risk. Keywords: COPD, exacerbation, FEV1, inspiratory capacity

Hye Sook Choi,1 Yong Bum Park,2,3 Kyeong Cheol Shin,4 Seung Hun Jang,3,5 Kang Hyeon Choe,6 Young Sam Kim,7 Sun Young Kyung,8 Sung Ho Yoon,9 Ju Sang Kim,10 Sung Soo Jung11 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital-Kangdong, Seoul, Republic of Korea; 3Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea; 4Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Republic of Korea; 5Division of Pulmonary, Allergy, and Critical Care Medicine, Department of 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, Chungbuk National University Hospital, Cheongju, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yonsei University Health System, Seoul, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, The Catholic University, Incheon St Mary’s Hospital, Incheon, Republic of Korea; 11Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea Background and objective: The Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Patient-Reported Outcomes (EXACT-PRO) has been suggested as a reliable and valid measure for early assessment of COPD exacerbations and perceived recovery. However, there has been no evidence for EXACT-PRO efficacy in assessing recovery from treatment in a randomized controlled trial. The study evaluated the reliability, validity, and responsiveness of EXACT-PRO for the evaluation of the efficacy of acute treatment in patients with COPD exacerbation.Methods: In a Phase III randomized controlled study for assessing the efficacy of antibiotic treatment on COPD exacerbation, EXACT-PRO was evaluated in the responders and non-responders.Results: A total of 295 patients were analyzed (259 responders and 37 non-responders). Cronbach’s α was 0.96 for EXACT total, 0.96 for the breathlessness domain, 0.89 for the cough and sputum domain, and 0.93 for the chest symptoms domain. The EXACT score correlated with the COPD assessment test (CAT) score (r=0.8, P

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

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

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon Min Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified.Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission.Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019).Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients. Keywords: acute exacerbation of COPD, Pseudomonas aeruginosa, readmission, bacterium, virus

Basheer Y Khassawneh,1 Shaher M Samrah,1 Mohamad I Jarrah,1 Rasheed K Ibdah,1 Ali M Ibnian,1 Abdelhameed W Almistarehi,1 Aseel A Zghayer,1 Saddam I Abuqudairi,1 Yousef S Khader2 1Department of Internal Medicine, Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Community Medicine, Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan Purpose: COPD and coronary artery disease (CAD) are common chronic diseases with shared risk factors. COPD continues to be largely underdiagnosed and undertreated. We aimed to describe the prevalence and predictors of undiagnosed COPD in Jordanian men with CAD. Patients and methods: In a cross-sectional study conducted at a referral center in Jordan, male patients who underwent coronary angiography for suspected CAD and reported ≥10 pack-year of cigarette smoking were recruited. Pre- and post-bronchodilator spirometry was undertaken for all participants, and COPD was defined as post-bronchodilator FEV1/FVC

Sung Woo Moon,1 Song Yee Kim,1 Ji Ye Jung,1 Young Ae Kang,1 Moo Suk Park,1 Young Sam Kim,1 Joon Chang,1 Jun Soo Ro,2 Yong-Ho Lee,3 Sang Hoon Lee1,4 1Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea; 2Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 3Division of Endocrinology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea; 4Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea Purpose: Previous studies have shown that progressive forms of non-alcoholic fatty liver disease (NAFLD) occur frequently in patients with obstructive lung disease (OLD). However, few studies have written about this relationship. This study aimed to investigate the relationship between OLD and NAFLD. Subjects and methods: The Korea National Health and Nutrition Examination Survey is a national population-based, cross-sectional surveillance program that was initiated to assess the health and nutritional status of the Korean population. From 2007 to 2010, 11,738 subjects were enrolled. The subjects were defined as having NAFLD when they had scores higher than -0.640 in a NAFLD liver fat score prediction model, which was a previously validated prediction score. Individuals with forced expiratory volume in one second/forced vital capacity

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

Youngmok Park, Ji Ye Jung, Young Sam Kim, Kyung Soo Chung, Joo Han Song, Song Yee Kim, Eun Young Kim, Young Ae Kang, Moo Suk Park, Joon Chang, Ah Young Leem Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea Background: Lung function and depression are closely related to many chronic lung diseases. However, few studies have evaluated this association in the general population. In this study, we evaluated the relationship between lung function and depression in the general population in Korea. Participants and methods: Data from the Ansung–Ansan cohort, a community-based cohort in Korea, were used to analyze the relationships between depression and lung function parameters. A total of 3,321 men and women aged 40–69 years were enrolled. Spirometry data included the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Depression was defined as a score of ≥16 by the Beck Depression Inventory (BDI). A propensity score analysis was conducted with the aim of reducing the bias of the retrospective study. Results: The overall prevalence of depression in the study population was 13.1% (434/3,321 participants). Depression was significantly more prevalent in women than in men (P

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

Chi Young Kim, Youngmok Park, Ah Young Leem, Kyung Soo Chung, Ji Ye Jung, Moo Suk Park, Young Sam Kim Division of Pulmonology, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea Background: Although studies have examined the relationship between metabolic syndrome (MetS) and COPD, the incidence of MetS in individuals with COPD has not specifically been investigated. This study aimed to evaluate the incidence of MetS in subjects with airway obstruction using data from a community-based cohort. Patients and methods: Data representing 4 years of follow-up from the Ansung–Ansan cohort were analyzed; a total of 6,184 adults, who were ≥40 years of age and underwent spirometry, were enrolled in this study. Airway obstruction was defined as forced expiratory volume in 1 s/forced vital capacity ratio

Ji-Hoon Lee, MinA Park, Myung Jae Park, Yong Suk Jo Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, KyungHee University Hospital, Seoul, Republic of Korea Background and objective: Although depression is considered one of the comorbidities of COPD, the clinical characteristics of depression in patients with early COPD remain unknown. We aimed to use national-level data to identify the clinical features and risk factors of depression in patients with early COPD. Methods: We examined 7,550 subjects who were registered in the Korean National Health and Nutrition Examination Survey database of 2014 because that was the only year in which the Patient Health Questionnaire-9 for depression status was administered. Spirometry was used to identify patients with COPD whose forced expiratory volume in 1 second was 50% or more, and these patients were included in the analysis. Results: Of the 211 subjects with early COPD, 14.2% also had depression, whereas 85.8% did not. The patients with depression were predominantly living alone and had a greater prevalence of diabetes compared with the patients without depression. The overall quality of life of the subjects with depression was lower than that of those without depression, and only the quality of life index correlated significantly with depression severity. In the multivariate regression analysis, female sex (adjusted OR, 1.79; 95% CI, 1.38–2.31; p

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

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Kyung Hoon Min, Gyu Young Hur, Sung Yong Lee, Kyung Ho Kang, Jae Jeong Shim Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events. Methods: We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea. Results: Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher [RR 1.612, 95% CI, 1.065–2.440, P=0.024]. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant [RR 1.003, 95% CI, 1.001–1.005, P=0.006]. Conclusion: Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high. Keywords: air pollution, particulate matter, air quality index, acute exacerbation, COPD

Ah Young Leem,1 Boram Park,2 Young Sam Kim,1 Ji Ye Jung,1 Sungho Won2 1Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, 2Department of Epidemiology and Biostatistics, School of Public Health, Seoul National University, Seoul, Korea Purpose: COPD is a leading cause of morbidity and mortality. However, few studies have used spirometry to investigate its incidence, especially in Asia. In the present study, we analyzed the incidence and risk factors of COPD using a community cohort database in Korea. Patients and methods: The study included 6,517 subjects aged 40–69 years from the Ansung–Ansan cohort database I–III (2001–2006). We calculated the crude incidence rate and the standardized incidence rate corrected for the Korean general population and the world population with COPD. We also determined the relative risks (RRs) for incident COPD and the attributable risks. Results: In total, 329 new COPD cases were diagnosed during follow-up. The overall crude incidence rate per 100,000 person-years was 1,447. The standardized incidence rate corrected for the Korean general population was 1,550; this value was higher in men and increased with increasing age. Risk factors for incident COPD were age ≥60 years (adjusted RR [aRR] =2.52 vs age

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

Yong Suk Jo,1 Ho Il Yoon,2 Deog Kyeom Kim,3 Chul-Gyu Yoo,1 Chang-Hoon Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Background and objective: Guidelines recommend the use of simple but comprehensive tools such as COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ) to assess health status in COPD patients. We aimed to compare the ability of CAT and CCQ to predict exacerbation in COPD patients. Methods: We organized a multicenter prospective cohort study that included COPD patients. The relationships between CAT, CCQ, and other clinical measurements were analyzed by correlation analysis, and the impact of CAT and CCQ scores on exacerbation was analyzed by logistic regression analyses and receiver operating characteristic curve. Results: Among 121 COPD patients, CAT and CCQ score correlated with other symptom measures, lung function and exercise capacity as well. Compared with patients who did not experience exacerbation, those who experienced exacerbation (n=45; 38.2%) exhibited more severe airflow limitation, were more likely to have a history of exacerbation in the year prior to enrollment, and demonstrated higher CAT scores. CCQ scores were not significantly associated with exacerbations. A CAT score of ≥15 was an independent risk factor for exacerbation (adjusted odds ratio [aOR], 2.40; 95% CI, 1.03–6.50; P=0.04). Furthermore, CAT scores of ≥15 demonstrated an increased predictive ability for exacerbation compared with currently accepted guidelines for the use of CAT (≥10) and CCQ (≥1) in the assessment of COPD patients (area under the curve for CAT ≥15, CAT ≥10, and CCQ ≥1 was 0.61±0.04, 0.53±0.03, and 0.50±0.03, respectively; P=0.03). Conclusion: A CAT score of ≥15 indicates increased risk of exacerbation in COPD patients, whereas there is no evidence for increased risk based on CCQ score. Keywords: COPD, exacerbation, questionnaire

Yogesh Suresh Punekar,1 John H Riley,2 Emily Lloyd,3 Maurice Driessen,2 Sally J Singh4 1Health Outcomes, GlaxoSmithKline, Uxbridge, 2MDC Global Clinical Development UK, Respiratory Research and Development, GlaxoSmithKline, Uxbridge, 3Value Evidence and Outcomes, GlaxoSmithKline, Brentford, 4Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Leicester, UK Introduction: Chronic obstructive pulmonary disease (COPD) is an increasingly common cause of death worldwide. Its cardinal symptoms include breathlessness and severely reduced exercise capacity. Several patient-reported outcome (PRO) measures are used to assess health-related quality of life (HRQoL), functional performance, and breathlessness in patients with COPD. Exercise testing is employed to measure functional performance objectively, which is generally believed to impact on overall HRQoL. However, the extent to which commonly used laboratory- and field-based exercise test results correlate with PROs has not been systematically assessed. Materials and methods: A search of Embase, MedLine, and the Cochrane Library identified primary publications in English that reported data on the correlations (Pearson’s r or Spearman’s Ρ) between the outcomes of exercise tests and HRQoL and breathlessness PROs. Studies reporting on the following tests were included: 6-minute walk test (6MWT), 12MWT, incremental and endurance shuttle walk tests, incremental and endurance cycle ergometer tests, and treadmill tests. Results: Of 3,205 articles screened, 28 were deemed eligible for inclusion. The most commonly reported HRQoL PRO measure was the St George’s Respiratory Questionnaire (13 studies), and the most commonly reported breathlessness PRO measure was the Baseline Dyspnea Index (six studies). The St George’s Respiratory Questionnaire appears to correlate very weakly to moderately with the 6MWT, and breathlessness PROs appear to be moderately to strongly associated with 6MWT outcomes. Across all studies, the 6MWT was the most commonly reported exercise test. Very few publications reporting associations between other exercise tests and PRO measures were found. Conclusion: This review found evidence to support the association of 6MWT outcomes with HRQoL and breathlessness PROs. There were limited data showing correlations with the outcomes of other exercise tests. Further work is required to examine the associations between these PROs and exercise test outcomes. Keywords: exercise tests, COPD, patient-reported outcomes

Yong Suk Jo,1 Ju-Hee Park,2 Jung Kyu Lee,2 Eun Young Heo,2 Hee Soon Chung,2 Deog Kyeom Kim2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Division 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, Republic of Korea Background and objective: There are limited data on pulmonary arterial hypertension (PAH) in patients with tuberculosis-destroyed lung (TDL), a sequela of pulmonary tuberculosis. We identified the risk factors for PAH and their effects on acute exacerbation and mortality in patients with TDL, as well as the clinical differences in patients with chronic obstructive pulmonary disease (COPD) and PAH.Methods: A retrospective cohort study was conducted from 2010 through 2015 in a municipal referral hospital in South Korea. PAH was defined when echocardiographic pulmonary arterial pressure (PAP) was >40 mmHg. The clinical features and course of TDL patients with or without PAH were evaluated and differences between patients with COPD and PAH were analyzed.Results: Among the 195 patients with TDL, echocardiographic data were available in 53 patients, and their mean PAP was 50.72±23.99 mmHg. The PAH group (n=37) had a smaller lung volume (forced vital capacity % predicted, 51.55% vs 72.37%, P

Yusheng Cheng,* Xiongwen Tu,* Linlin Pan, Shuai Lu, Ming Xing, Linlin Li, Xingwu Chen Department of Respiratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China *These authors contributed equally to this work Purpose: Chronic bronchitis (CB), emphysematous (EM) and asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized. This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE).Patients and methods: A retrospective study was carried out. COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016. Patients were divided into FE and infrequent exacerbations (iFE) subgroups.Results: A total of 142 eligible COPD subjects were reviewed. In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB. In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE. Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype. No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE.Conclusion: In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation. Keywords: chronic bronchitis, emphysema, ACOS, COPD, frequent exacerbations

Cheong-Ju Kim,1 Hyoung-Kyu Yoon,2 Myung-Jae Park,3 Kwang-Ha Yoo,4 Ki-Suck Jung,5 Jeong-Woong Park,6 Seong Yong Lim,7 Jae Jeong Shim,8 Yong Chul Lee,9 Young-Sam Kim,10 Yeon-Mok Oh,11 Song Kim,12 Chul-Gyu Yoo13 1Department of Internal Medicine, National Health Insurance System Ilsan Hospital, Koyang, 2Division of Pulmonology, Department of Internal Medicine, St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Respiratory and Critical Care Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, 4Department of Internal Medicine, Konkuk University School of Medicine, Gwangjin-gu, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang-si, 6Division of Pulmonary and Allergy Medicine, Gachon University Gil Medical Center, Incheon, 7Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 8Department of Internal Medicine, Korea University College of Medicine, Seoul, 9Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonbuk, 10Department of Internal Medicine, Yonsei University College of Medicine, 11Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 12Clinical Development and Medical Affairs, Novartis Korea Ltd., Seoul, 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Background and objective: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. Methods: This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George’s Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks. Results: Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P

Yipeng Ding,* Heping Xu,* Jinjian Yao, Dongchuan Xu, Ping He, Shengyang Yi, Quanni Li, Yuanshui Liu, Cibing Wu, Zhongjie Tian Department of Emergency, People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Objective: We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 (RTEL1), which has been associated with telom­ere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population.Methods: In a case–control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender.Results: In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10–0.82; P=0.02). In the genetic model analysis, we found that the “C/C” genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13–0.86; P=0.022) and recessive model (OR =0.32; 95% CI =0.12–0.80; P=0.009).Conclusion: Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population. Keywords: RTEL1, chronic obstructive pulmonary disease, COPD, gene polymorphisms, association study, case-control study

Yan-xia Tao,1,* Lan Wang,1,* Xiao-yan Dong,1 Hong Zheng,2 Ya-shu Zheng,2 Xing-yue Tang,1 Yue Zhao,1 Qing Zhang1 1School of Nursing, Tianjin Medical University, 2Department of Respiratory Care, Tianjin First Center Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Background: For patients with COPD, physical activity (PA) is recommended as the core component of pulmonary rehabilitation, but there is lack of a validated questionnaire for assessing the PA effectively. Aim: To evaluate the reliability and validity of the Chinese version of Physical Activity Scale for the Elderly (PASE-C) in patients with COPD. Methods: A cross-sectional study was conducted with 167 outpatients aged 60 years or older with COPD. Test-retest reliability and internal consistency were calculated by intraclass correlation coefficient (ICC) and Cronbach’s coefficient α, respectively. Validity was evaluated by correlation with the International Physical Activity Questionnaire-Short (IPAQ-S), data of pedometer, Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), grip strength, and disease characteristics. Results: The PASE-C had an excellent seven-day test-retest reliability (ICC=0.98) and an acceptable internal consistency (Cronbach’s α=0.71). The content validity was supported by an item-content validity index, a scale-content validity index/universal agreement, and a scale-content validity index/average value of 0.70-1, 0.70, and 0.93, respectively. Concurrent validity was tested by correlation with IPAQ-S (r=0.651). Criterion validity was confirmed by correlation with the walking steps (r=0.611) and energy expenditure (r=0.493). For construct validity, PASE-C had correlations with SES6 (r=0.396), HADS for depression (r=-0.234), seven subscales of SF-36 (r=0.182-0.525), grip strength (r=0.341), and disease characteristics including the duration of COPD (r=-0.215), modified British Medical Research Council scale (r=-0.354), forced expiratory volume in one second as percentage of predicted (r=0.307), and Global Initiative for Chronic Obstructive Lung Disease grade (r=-0.264), with a good construct validity (all P

Chan Ho Lee, Eun Kyung Goag, Su Hwan Lee, Kyung Soo Chung, Ji Ye Jung, Moo Suk Park, Young Sam Kim, Se Kyu Kim, Joon Chang, Joo Han Song Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. Materials and methods: Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. Results: The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. Conclusion: Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity. Keywords: airway obstruction, ferritin, smoking

Zhiwei Lu,* Yusheng Cheng,* Xiongwen Tu, Liang Chen, Hu Chen, Jian Yang, Jinyan Wang, Liqin Zhang Department of Respiratory Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to appraise the effect of community-acquired pneumonia (CAP) on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD) patients admitted to a respiratory intensive care unit.Patients and methods: A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann–Whitney U-test. Kaplan–Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox’s proportional hazards regression model was performed to identify risk factors for multivariate analysis.Results: A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P

Kyung Soo Chung,1,2 Ji Ye Jung,1,2 Moo Suk Park,1,2 Young Sam Kim,1,2 Se Kyu Kim,1,2 Joon Chang,1,2 Joo Han Song1,2 1Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) has been proposed as an alternative to FEV1/forced vital capacity (FVC) for detecting airway obstruction. A fixed cut-off value for FEV1/FEV6 in a Korean population is lacking. We investigated a fixed cut-off for FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction.Materials and methods: We used data obtained in the 5 years of the Fifth and Sixth Korean National Health and Nutrition Examination Survey. A total of 14,978 participants aged ≥40 years who underwent spirometry adequately were the study cohort. “Airway obstruction” was a fixed cut-off FEV1/FVC

Eun Sun Kim,1 Young Tae Kim,2 Chang Hyun Kang,2 In Kyu Park,2 Won Bae,1 Sun Mi Choi,1 Jinwoo Lee,1 Young Sik Park,1 Chang-Hoon Lee,1 Sang-Min Lee,1 Jae-Joon Yim,1 Young Whan Kim,1 Sung Koo Han,1 Chul-Gyu Yoo1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose: This study aimed to investigate whether the prevalence of postoperative pulmonary complications (PPCs) in patients with non-small-cell lung cancer (NSCLC) is even higher in the early stages of COPD than in such patients with normal lung function and to verify the usefulness of symptom- or quality of life (QoL)-based scores in predicting risk for PPCs.Patients and methods: Patients undergoing pulmonary resection for NSCLC between July 2012 and October 2014 were prospectively enrolled. Preoperative measurements of lung function, dyspnea, and QoL, operative characteristics, PPCs, duration of postoperative hospitalization, and in-hospital mortality were assessed.Results: Among 351 consecutive patients with NSCLC, 343 patients with forced expiratory volume in 1 second (FEV1) ≥70% of predicted value were enrolled. At least one PPC occurred in 57 (16.6%) patients. Prevalence of PPC was higher in patients with COPD (30.1%) than in those with normal spirometry (10.0%; P

Kang-Hyun Kim,1 Tai Sun Park,2,3 You-Sun Kim,1,3 Jae Seung Lee,2,3 Yeon-Mok Oh,2,3 Sang-Do Lee,2,3 Sei Won Lee2,3 1Asan Institute for Life Sciences, 2Department of Pulmonology and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, 3Department of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea Purpose: Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration.Materials and methods: C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid.Results: Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking.Conclusion: RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. Keywords: resolvin D1, COPD, emphysema

Youngmok Park,1 Young Sam Kim,1 Young Ae Kang,1 Ju Hye Shin,1 Yeon Mok Oh,2 Joon Beom Seo,3 Ji Ye Jung,1 Sang Do Lee2 On behalf of the KOLD study 1Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Institute of Chest Diseases, Yonsei University College of Medicine, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, 3Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background: In chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD. Methods: The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL. Results: The mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level. Conclusion: The GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD. Keywords: vitamin D-binding protein, polymorphism, vitamin D, chronic obstructive pulmonary disease

Sei Won Lee,1 Hyun Kuk Kim,2 Seunghee Baek,3 Ji-Ye Jung,4 Young Sam Kim,4 Jae Seung Lee,1 Sang-Do Lee,1 David M Mannino,5 Yeon-Mok Oh1 1Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 2Department of Pulmonary and Critical Care Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, 3Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 4Division of Pulmonary, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 5Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY, USA Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score. Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years. Results: The probability of all-cause death appeared to remain nearly zero until -1 of forced expiratory volume in 1 second (FEV1) T-score but increased steeply where FEV1 T-score reached below -2.5. Survival curves for all-cause death, respiratory death, COPD death, and COPD utilization differed significantly among the groups when stratified by FEV1 T-score (P

Hyung-Jun Kim,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Sang-Min Lee,1,2 Jae-Joon Yim,1,2 Chul-Gyu Yoo,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Sun Mi Choi1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose: Chronic obstructive pulmonary disease (COPD) is associated with increased postoperative complications. Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classified COPD patients into four groups based on spirometry results and the severity of symptoms. The objective of this study was to evaluate the impact of GOLD groups on postoperative complications. Patients and methods: We reviewed the medical records of COPD patients who underwent preoperative spirometry between April and August 2013 at a tertiary hospital in Korea. We divided the patients into GOLD groups according to the results of spirometry and self-administered questionnaires that assessed the symptom severity and exacerbation history. GOLD groups, demographic characteristics, and operative conditions were analyzed. Results: Among a total of 405 COPD patients, 70 (17.3%) patients experienced various postoperative complications, including infection, wound, or pulmonary complications. Thoracic surgery, upper abdominal surgery, general anesthesia, large estimated blood loss during surgery, and longer anesthesia time were significant risk factors for postoperative complications. Patients in high-risk group (GOLD groups C or D) had an increased risk of postoperative complications compared to those in low-risk group (GOLD groups A or B). Conclusion: COPD patients in GOLD groups representing a high exacerbation risk have an increased risk of postoperative complications compared to those with low risk. Keywords: chronic obstructive pulmonary disease, dyspnea, postoperative complications, risk assessment, spirometry

Soo Jung Kim,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Ho Il Yoon,1,3 Sang-Min Lee,1,2 Jae-Joon Yim,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Chul-Gyu Yoo1,2 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea Background: According to the Fletcher–Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases. However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients. The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients. Methods: In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of

Afisi Segun Ismaila,1,2 Eline L Huisman,3 Yogesh Suresh Punekar,4 Andreas Karabis31Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands; 4Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UKBackground: Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).Methods: A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.Results: Twenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]); 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]); 24-week St George’s Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to -2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]); 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]); and 24-week rescue medication use (data not available; -0.41 puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0.74 to -0.30]; -0.30 puffs/day [-0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were -12.8 mL (-39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (-7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (-11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (-11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (-5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (-15.30 to 54.38), umeclidinium versus glycopyrronium. Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.Conclusion: The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard. Choice should depend on physician’s and patient’s preference.Keywords: anticholinergics, muscarinic antagonist, bronchodilator, systematic review, meta-analysis

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

Ha Youn Lee,1,2 Sun Mi Choi,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Deog Kyeom Kim,2,3 Sang-Min Lee,1,2 Ho Il Yoon,2,4 Jae-Joon Yim,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Chul-Gyu Yoo1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with

Eline L Huisman,1 Sarah M Cockle,2 Afisi S Ismaila,3,4 Andreas Karabis,1 Yogesh Suresh Punekar2 1Mapi Group, Real World Strategy and Analytics and Strategic Market Access, Houten, the Netherlands; 2Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK; 3Value Evidence and Outcomes, GlaxoSmithKline R&D, Research Triangle Park, NC, USA; 4Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Background: Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable. This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers. Methods: A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers. Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework. Results: A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 µg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: -14.2, 42.3]), SGRQ total score (0.18 [-1.28, 1.63]), TDI focal score (-0.30 [-0.73, 0.13]), and rescue medication use (0.02 [-0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [-25.3, 159.4]), SGRQ total score (-0.11 [-1.84, 1.61]), and TDI focal score (0.58 [-0.33, 1.50]); and compared with formoterol plus TIO 18 µg on SGRQ total score (-0.68 [-1.77, 0.39]). Results at week 12 were consistent with week 24 outcomes. Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks. Conclusion: UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints. Keywords: LABA/LAMA, UMEC/VI, QVA149, fomoterol, tiotropium, glycopyrronium, indacaterol, umeclidinium