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Ye-Jin Lee,1 SeungHo Choi,2 Sung-Youn Kwon,2 Yunhwan Lee,2 Jung Kyu Lee,3 Eun Young Heo,3 Hee Soon Chung,3,4 Deog Kyeom Kim3,4 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 2Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984 Korea; 3Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea; 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Deog Kyeom KimDivision of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Boramae-Gil 41, Dongjak-gu, Seoul 156-707, Republic of KoreaTel +82-2-870-3207Fax +82-2-831-0714Email kimdkmd@gmail.comBackground: Identifying the genetic basis of airflow limitation is one of the most interesting issues for understanding chronic obstructive pulmonary disease (COPD) pathophysiology. Several studies have shown that some genetic variants associated with COPD have been identified in genome-wide association study (GWAS), especially in patients with moderate to severe COPD; genetic susceptibility for airflow limitation in the early COPD phase has not been widely studied.Objective: We investigated the genetic variants in early COPD.Methods: The present study analyzed Gene-environment interaction and phenotype (GENIE) cohort that included participants who received health screening examination. The association between single nucleotide polymorphism (SNP) and susceptibility to early COPD (FEV1 predicted ≥ 50% and FEV1/FVC < 0.7) was tested.Results: A total of 130 patients with early COPD and 3478 controls (1700 ever smokers and 1778 never smokers) were recruited. When compared with the total controls, certain SNPs (rs2818103, rs875033, rs9354627, rs34552148) on chromosome 6 were included at the top of our list (p= 5.6 × 10– 7 ∼ 9.6 × 10– 6) although they did not reach genome-wide significance. When compared with the never smoker controls, two SNPs (rs2857210, rs2621419) of the HLA-DQB2 gene class were persistently associated with susceptibility to early COPD.Conclusion: Certain SNPs located on chromosome 6 or the HLA-DQB2 gene were the top-scoring SNPs for the association with susceptibility to early COPD in the Korean GENIE cohort.Keywords: early chronic obstructive pulmonary disease, genome-wide association study, single nucleotide polymorphism, SNP, HLA-DQ gene

Jung-Ki Yoon,1 Jung-Kyu Lee,2 Chang-Hoon Lee,1 Yong Il Hwang,3 Hyunkuk Kim,4 Dongil Park,5 Ki-Eun Hwang,6 Sang-Heon Kim,7 Ki-Suck Jung,3 Kwang Ha Yoo,8 Seung Won Ra,9 Deog Kyeom Kim2,10 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 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, Republic of Korea; 3Department of Internal Medicine, College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Republic of Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea; 6Department of Internal Medicine, Wonkwang University, School of Medicine, Iksan, Republic of Korea; 7Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea; 9Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 10Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Deog Kyeom KimDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of KoreaTel +82-2-870-2228Fax +82-2-831-0714Email kimdkmd@snu.ac.krIntroduction: Blood eosinophils are a predictive marker for the use of inhaled corticosteroids (ICS). However, there is concern over whether a single measure of blood eosinophils is sufficient for outlining a treatment plan. Here, we evaluated the association between variability in blood eosinophils and the effects of ICS in stable COPD cohorts.Methods: COPD patients in the Korean COPD Subtype Study and the Seoul National University Airway Registry from 2011 to 2018 were analyzed. Based on blood eosinophils at baseline and at 1-year follow-up, the patients were classified into four groups with 250/μL as a cutoff value: consistently high (CH), consistently low (CL), variably increasing (VI), and variably decreasing (VD). We compared rates of acute exacerbations (AEs) according to ICS use in each group after calibration of severity using propensity score matching.Results: Of 2,221 COPD patients, 618 were analyzed and a total of 125 (20%), 355 (57%), 63 (10%), and 75 (12%) patients were classified into the CH, CL, VI, and VD groups, respectively. After calibration, we found that ICS users tended to have a lower AE rate in the CH group (RR 0.41, 95% CI 0.21– 0.74) and VI group (RR 0.45, 95% CI 0.22– 0.88), but not in the CL group (RR 1.42, 95% CI 1.08– 1.89) and VD group (RR 1.71, 95% CI 1.00– 2.96).Conclusion: More than one-fifth of patients had an inconsistent blood eosinophil level after the 1-year follow-up, and the AE-COPD rate according to ICS differed based on variability in eosinophils. Regular follow-up of blood eosinophils is required for COPD patients.Keywords: COPD, eosinophils, inhaled corticosteroids, acute exacerbations of COPD, COPD treatment

Ha Youn Lee,1,2 Ji Won Kim,2,3 Jung Kyu Lee,2,4 Eun Young Heo,2,4 Hee Soon Chung,2,4 Deog Keom Kim2,4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 2Department of Internal Medicine, Seoul National University College of Medicine, 3Division of Gastroenterology, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Background: Helicobacter pylori infection is a major cause of gastric diseases. The clinical implications of H. pylori infection in various diseases outside the gastrointestinal system have also been reported, including in some respiratory disorders. In this study, we investigated the seroprevalence of H. pylori in patients with mild to moderate COPD in an Asian country with a high prevalence of H. pylori infection. Also, we aimed to elucidate the association between the seroprevalence of H. pylori and the decline of lung function in patients with COPD.Methods: Participants who underwent a medical checkup for H. pylori at a referral hospital in Korea were recruited for this study. All participants were tested for H. pylori infection using an immunoassay of the H. pylori-specific immunoglobulin G (IgG) concentration and a rapid urease test at the time of endoscopy with a gastric mucosal specimen. We assessed the decline in lung function using the spirometric data of those who underwent spirometry more than three times.Results: In total, 603 participants (201 patients with COPD and 402 controls) were analyzed. The seroprevalence of H. pylori IgG in the patients and controls was 45.8% and 52.2%, respectively (P=0.134). The H. pylori IgG level in patients with COPD was not significantly different from that of the controls (114.8 and 109.6 units/mL, respectively; P=0.549). In addition, there were no significant differences in the annual forced expiratory volume in 1 second or forced vital capacity between the participants with H. pylori seropositivity and seronegativity.Conclusion: This study showed no relationship between H. pylori infection and COPD in a country with a high burden of H. pylori infection. Furthermore, H. pylori infection did not affect the rate of lung function decline in this study population. Keywords: H. pylori, COPD, lung function decline