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The control of the in-plane domain evolution in ferroelectric thin films is not only critical to understanding ferroelectric phenomena but also to enabling functional device fabrication. However, in-plane polarized ferroelectric thin films typically exhibit complicated multi-domain states, not desirable for optoelectronic device performance. Here we report a strategy combining interfacial symmetry engineering and anisotropic strain to design single-domain, in-plane polarized ferroelectric BaTiO3 thin films. Theoretical calculations predict the key role of the BaTiO3/PrScO3 [Formula: see text] substrate interfacial environment, where anisotropic strain, monoclinic distortions, and interfacial electrostatic potential stabilize a single-variant spontaneous polarization. A combination of scanning transmission electron microscopy, piezoresponse force microscopy, ferroelectric hysteresis loop measurements, and second harmonic generation measurements directly reveals the stabilization of the in-plane quasi-single-domain polarization state. This work offers design principles for engineering in-plane domains of ferroelectric oxide thin films, which is a prerequisite for high performance optoelectronic devices.

Phase mixture single layer film with 3-dimensional spatial distribution of internal interfaces between ferromagnetic and antiferromagnetic nanoclusters was achieved through the inhomogeneous distribution of oxygen atoms within the ferromagnetic transition metal thin film layer. In the present work, enhanced exchange bias properties of phase mixture single layer film including both exchange and super-exchange couplings within the body of the single layer were investigated under various conditions. The film exhibited same exchange bias field regardless of the layer thickness, which violates the known relationship of inverse proportionality between the exchange bias field and the thickness of the magnetic layer in the conventional ferromagnet/antiferromagnet bilayers systems. Furthermore, it was found that the exchange bias could be set in any direction with respect to the film surface, removing the restriction by the magnetic shape anisotropy of the thin film structure. Low blocking temperature of the phase mixture single layer film could also be overcome with an additional neighboring antiferromagnet layer.

Eun Hye Lee,1,* Hyun Tae Kim,2,* So Young Chun,3 Jae-Wook Chung,2 Seock Hwan Choi,2 Jun Nyung Lee,2 Bum Soo Kim,2 Eun Sang Yoo,2 Tae Gyun Kwon,2 Tae-Hwan Kim,2 Yun-Sok Ha2 1Joint Institution of Regenerative Medicine, Kyungpook National University, Daegu, Korea; 2Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea; 3BioMedical Research Institute, Kyungpook National University Hospital, Daegu, Korea*These authors contributed equally to this workCorrespondence: Tae-Hwan Kim; Yun-Sok Ha, Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea, Email doctork@knu.ac.kr; Koreayunsokha@gmail.comAbstract: Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer.Keywords: bladder cancer, JNK, proliferation, apoptosis, metastasis, chemoresistance, autophagy

So Ron Choi, Deuk Won Eom, Tae Young Lee, Ji Wook Jung, Gang Hyun Lee, Seung Cheol Lee, Sang Yoong Park, Tae Hyung Kim Department of Anesthesiology and Pain Medicine, University of Dong-A College of Medicine, Busan, Republic of KoreaCorrespondence: Sang Yoong Park, Department of Anesthesiology and Pain Medicine, University of Dong-A College of Medicine, 26 Daeshingongwon-ro, Seo-gu, Busan, 49201, Republic of Korea, Tel +82-51-240-5390, Fax +82-51-247-7819, Email parksy@dau.ac.krAbstract: Tracheal tumor resection and reconstruction is the primary treatment for tracheal tumors. The trachea is the surgical site as well as an important channel to ensure ventilation and maintain oxygenation during surgery. In this report, we describe the successful management of an upper tracheal tumor in a 50-year-old patient. The tumor was situated approximately 2– 3 cm below the vocal cords, occluding the tracheal lumen by 80%. Conventional orotracheal intubation was expected to be impossible, and the patient was managed with an I-Gel supraglottic airway for mechanical ventilation with the assistance of venovenous extracorporeal membrane oxygenation (VV ECMO). After securing tracheal intubation via the tracheostomy site, VV ECMO was weaned off, and mechanical ventilation was changed to tracheal intubation. Eventually, tracheal tumor resection and reconstruction were successfully performed under general anesthesia. No specific events occurred during anesthetic management. Careful preoperative planning and good teamwork made the procedure possible without complications.Keywords: anesthesia, extracorporeal membrane oxygenation, tracheal resection and reconstruction

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

Youlim Kim,1,&ast; Hyun Lee,2,&ast; Sung Jun Chung,2,&ast; Yoomi Yeo,2 Tai Sun Park,2 Dong Won Park,2 Kyung Hoon Min,3 Sang-Heon Kim,2 Tae-Hyung Kim,2 Jang Won Sohn,2 Ji-Yong Moon,2 Ho Joo Yoon2 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Korea; 2Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea; 3Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Medical Center, Guro Hospital, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Yong MoonDepartment of Internal Medicine, Hanyang University Guri Hospital, Gyeongchun-ro 153, Guri-si, Gyeonggi-do, 11923, KoreaTel +82-31-560-2224Fax +82-31-553-7369Email respiry@gmail.comHo Joo YoonDivision of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, KoreaTel +82-2-2290-8336Fax +82-2-2298-9183Email hjyoon@hanyang.ac.krBackground and Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF25– 75), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF25– 75 in predicting AHR has not been well elucidated. Therefore, we investigated whether FEF25– 75 can predict AHR to mannitol.Methods: We performed a retrospective cohort study of 428 patients who visited a single clinic due to cough, wheezing, or dyspnea. All patients underwent spirometry with a mannitol provocation test. We compared the area under the curve (AUC) of the percentage of the predicted values of FEF25– 75 (FEF25– 75 %pred) with that of forced expiratory volume in 1 second (FEV1%pred), FEV1/forced vital capacity (FVC), and FEF25– 75/ FVC for predicting AHR.Results: The rate of AHR to mannitol was 20.3%. In the overall study population, the AUC of FEF25– 75 %pred for predicting AHR (0.772; 95% confidence interval [CI], 0.729– 0.811) was significantly higher than that of FEV1%pred (0.666; 95% CI, 0.619– 0.710; p < 0.001), FEV1/FVC (0.741; 95% CI, 0.697– 0.782; p = 0.047), and FEF25– 75/FVC (0.741, 95% CI = 0.696– 0.782, p = 0.046). The sensitivity, specificity, positive predictive value, and negative predictive value of FEF25– 75 %pred < 81% for predicting AHR in the overall study population were 77.0% (95% CI = 66.8– 85.4%), 63.9% (95% CI = 58.6– 69.0), 35.3%, and 91.6%, respectively. When we restricted the study group to subjects with normal lung function, the results were similar.Conclusion: Our results indicate that FEF25– 75 %pred can be used as a surrogate for predicting AHR in patients with respiratory symptoms.Keywords: forced expiratory flow between 25% and 75% of vital capacity, mannitol, bronchial hyperresponsiveness

Kangpyo Kim,1 Tae Hyung Kim,1 Tae Hyun Kim,2 Jinsil Seong1 1Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Statistics, University of Chicago, Chicago, IL, USACorrespondence: Jinsil SeongDepartment of Radiation Oncology, Yonsei University College of Medicine, Seoul, 03722, Republic of KoreaTel + 82-2-2228-8111Fax + 82-2-2227-7823Email jsseong@yuhs.acPurpose: With respect to various solid cancers, patients with oligometastasis may benefit from local therapy. However, this approach is not widely accepted for hepatocellular carcinoma. This study investigated the efficacy of local therapy for oligometastatic lesions in patients with hepatocellular carcinoma.Patients and Methods: The study included 69 hepatocellular carcinoma patients presenting with oligometastasis to the lung. Characteristics of the patients and treatment options for metastatic lesions were reviewed, and a survival analysis was performed. After propensity score matching, overall survival and progression-free survival were calculated from the time of pulmonary metastasis detection. Factors predicting prognosis were analyzed using a multivariate Cox regression analysis.Results: After propensity score matching, 58 patients with Child-Pugh grade A disease were selected. Among them, 22 patients were treated with systemic therapy alone while 36 patients received local therapy or a combination of local and systemic therapies for metastatic lesions. Survival rates were higher in patients receiving local therapy than in those receiving systemic therapy (2-year overall survival rate, 66.6 vs 31.2%, p< 0.001; 2-year progression-free survival rate, 47.0 vs 10.6%, p=0.005). In the multivariate Cox regression analysis, alpha-fetoprotein levels less than 400 ng/mL and the use of local therapy for metastatic lesions were found to be significant favorable prognostic factors.Conclusion: Local therapy for metastatic lesions improved the oncologic outcomes of patients with hepatocellular carcinoma with pulmonary oligometastasis.Keywords: HCC, local ablation therapy, oligometastasis, propensity score matching

Hyeok Jun Goh,1 Ki Soo Lee,1 Tae Hyo Kim,1 Kyu Nam Kim,2 Hyun Jin Lim,2 Kyu Shik Kim,3 Won Jae Yang,4 Jung Ki Jo3 1Department of Urology, Dong-A University, College of Medicine, Busan, Korea; 2Department of Anesthesia and Pain Medicine, Hanyang University, College of Medicine, Seoul, Korea; 3Department of Urology, Hanyang University, College of Medicine, Seoul, Korea; 4Department of Urology, Soonchunghyang University Hospital, Seoul, KoreaCorrespondence: Jung Ki JoDepartment of Urology, Hanyang University, College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, KoreaTel +821025196241Email victorjo38@hanyang.ac.krPurpose: Postoperative anemia is associated with increased morbidity and mortality in patients undergoing surgery. Anemia is also a common feature during sepsis. Therefore, here, we aimed to investigate the safety and efficacy of intravenous iron isomaltoside 1000 (Monofer®) in patients undergoing elective urologic surgery and in those with urosepsis.Materials and Methods: This multicenter study was conducted through the review of the medical records of patients with postoperative anemia undergoing elective urologic surgery or with urosepsis in a multicenter hospital. Patients received a single intravenous iron isomaltoside (IIM), and their hemoglobin (Hb) level was evaluated before and after administration of IIM. Safety data included adverse effects and hypersensitivity reactions. In addition, the patients were divided into three groups (200 mg, 400 mg, and 600 mg IIM) to compare Hb changes before and after the administration of IIM.Results: The study analyzed 52 men and 30 women with a mean age of 67 years. There was a significant difference between pre-treatment Hb and post-treatment Hb according to the type of the surgery after administration (p=0.01) of IIM in patients with postoperative anemia, and the mean preoperative Hb before IIM administration was 8.5 g/dL and that after IIM administration was 9.9 g/dL (p=0.006) in patients with urosepsis. The mean preoperative Hb changed from 10 g/dL to 11 g/dL after administration (p< 0.001) of IIM in the whole cohort. There were no side effects due to the administration of intravenous IIM.Conclusion: A single perioperative intravenous injection of IIM 1000 significantly increased the Hb level in patients with anemia who underwent urologic elective surgery. Moreover, this treatment can be considered to have potential clinical benefits for anemia caused by sepsis.Keywords: anemia, iron, iron isomaltoside 1000, urosepsis

Do Sun Kwon,1,* Yong Jun Choi,2,* Tae Hee Kim,2 Min Kwang Byun,2 Jae Hwa Cho,2 Hyung Jung Kim,2 Hye Jung Park2 1Department of Internal Medicine, Hallym Hospital, Incheon, Korea; 2Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea*These authors contributed equally to this workCorrespondence: Hye Jung Park Department of Internal MedicineGangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul 60273, Republic of KoreaTel +82-2-2019-3302Fax +82-2-3463-3882Email craft7820@yuhs.acPurpose: The forced mid-expiratory flow (FEF25-75%) value is a potentially sensitive marker of obstructive peripheral airflow. We aimed to assess whether FEF25-75% can be an early predictor of chronic obstructive pulmonary disease (COPD).Patients and Methods: Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital. We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later. A FEF25-75% z-score less than − 0.8435 was considered low. We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019.Results: Among 307 patients, 91 (29.6%) had low FEF25-75% at baseline. After 10 years, the incidence rate of COPD in the low FEF25-75% group was significantly higher than that in the normal FEF25-75% group (41.8% vs 7.4%; P-value< 0.001). The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; P-value< 0.001), smoking status (occasional smoker HR, 4.59; P-value< 0.001 and long-term smoker HR, 2.18; P-value=0.023), and low FEF25-75% (HR, 3.31; P-value< 0.001) were predictive factors for the development of COPD.Conclusion: The FEF25-75% value in patients with normal lung function is a useful predictor for the development of COPD. We should carefully monitor patients who present with low FEF25-75% values, even if they have normal lung function.Keywords: COPD, respiratory function tests, tobacco

Kyung-Hwa Kwak,1 Seung Ik Baek,1 Jay Kyoung Kim,1 Tae-Hwan Kim,2 Jinseok Yeo1 1Department of Anesthesiology and Pain Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, Korea; 2Department of Urology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, KoreaCorrespondence: Jinseok YeoDepartment of Anesthesiology and Pain Medicine, Kyungpook National Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, KoreaTel +82 53-200-2644Fax +82 53-200-2027Email painfree@gmail.comPurpose: The quadratus lumborum block (QLB) is a relatively new regional analgesic technique that could provide analgesia to the abdominal wall and reduce postoperative opioid consumption. We investigated the opioid-sparing effect of a unilateral lateral QLB in laparoscopic nephrectomy.Patients and Methods: A total of 60 patients undergoing laparoscopic nephrectomy were included in the study. Patients were randomized into two groups as QLB and control group. QLB group received QLB with 25mL 0.25% ropivacaine, and the control group received 25mL 0.9% saline at anterolateral border of quadratus lumborum muscle preoperatively. Opioid consumption and the pain intensity at rest and on movement were measured at 2nd, 6th, 24th, and 48th hour postoperatively. We also assessed the time to first flatus to measure the extent of paralytic ileus and the quality of recovery-15 (QoR-15) questionnaire.Results: Postoperative opioid consumption was significantly lower in the QLB group than in the control group at 6, 24, and 48h after surgery (P < 0.05). The pain intensity at rest and on movement was significantly lower in the QLB group than in the control group during the first 24 hours after surgery (P < 0.05). The incidence of postoperative nausea and vomiting, time to first flatus, and QoR-15 score did not show significant differences.Conclusion: Preoperative unilateral QLB successfully decreased postoperative pain and opioid consumption after laparoscopic nephrectomy and could be an option for analgesia after laparoscopic nephrectomy.Keywords: quadratus lumborum block, laparoscopic nephrectomy, postoperative pain, opioid consumption, ultrasound-guided block

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

Mi-Ae Kim,1 Min-Kang Suh,1 Jisoo Park,1 Jung-Hyun Kim,1 Tae-Hoon Kim,1 Eun Kyung Kim,1 Yeon-Mok Oh,2 Sang-Do Lee,2 Ji-Hyun Lee1 1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Ji-Hyun LeeDepartment of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 463-712, Republic of KoreaTel +82 31 780 5205Fax +82 31 780 2992Email plmjhlee@cha.ac.krPurpose: We compared clinical characteristics of COPD patients according to symptom variability and evaluated the effect of symptom variability during the first year of enrollment on clinical outcomes of COPD.Methods: We analyzed COPD patients’ data from the Korean Obstructive Lung Disease (KOLD) cohort. Symptom variability was defined based on the value of standard deviation (SD) of mMRC scores obtained every 3 months during the follow-up period of the first year. Patients were divided into 2 groups: the consistent (SD of mMRC scores =0) and variable (SD of mMRC scores >0) groups. Clinical characteristics and outcomes were compared in terms of symptom variability.Results: A total of 407 patients were included in the analysis. Patient age was 67.2 years and 97.8% of the subjects were male. Initial mMRC was 1.5 and the SD of mMRC scores during the first year was 0.5. There were 137 subjects (33.7%) in the consistent group and 270 (66.3%) in the variable group. The variable group showed a lower FEV1 (P=0.019) and a higher mMRC score (P=0.001). The annual incidence of acute exacerbation of COPD (AE-COPD) tended to be higher in the variable group (P=0.078) and that of severe AE-COPD was higher in the variable group than in the consistent group (P=0.002). The variable group showed a higher proportion of annual exacerbators (P=0.001) and frequent exacerbators (P=0.017). In multivariate logistic regression analysis, the variable group was significantly associated with annual exacerbators (OR =1.963, P=0.011) and frequent exacerbators (OR =2.090, P=0.055).Conclusion: COPD patients with symptom variability may have higher exacerbation risk as well as lower lung function and more severe respiratory symptoms.Keywords: COPD, symptom, variability, exacerbation, death, lung function

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

Kiok Kim,1,* Kyung-Min Shin,2,* Christy L Hunt,3 Zhen Wang,4 Brent A Bauer,5 Ojin Kwon,2 Jun-Hwan Lee,2,6 Bok-Nam Seo,7 So-Young Jung,2 Yousuk Youn,1 Sang Ho Lee,1 Jung Chul Choi,1 Jae Eun Jung,8 Jaehong Kim,1 Wenchun Qu,3,9 Tae-Hun Kim,10 Jason S Eldrige9 1Department of Spine Center, Mokhuri Neck & Back Hospital, Seoul, South Korea; 2Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 3Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 4Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 5Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 6Korean Medicine Life Science, Campus of Korea Institute of Oriental Medicine, University of Science & Technology (UST), Daejeon, South Korea; 7Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 8Hongik Neurosurgery Hospital, Seongnam, South Korea; 9Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 10Korean Medicine Clinical Trial Center, Korean Medicine Hospital, Kyung Hee University, Seoul, South Korea *These authors contributed equally to this work Background: Lumbar spinal stenosis (LSS) is a chronic condition that causes low back pain and neurogenic claudication, often resulting in significant limitation of daily activities. In this open-label randomized controlled pilot study, we assessed the safety and feasibility of 4-week novel integrative inpatient treatments for LSS. Methods: Thirty-six symptomatic LSS patients were randomly and equally allocated to one of the three groups: Mokhuri Chuna treatment 1 (MT1) group, Mokhuri Chuna treatment 2 (MT2) group, or conventional management treatment (CMT) group. MT1 patients were treated with herbal medication, Mokhuri Chuna, and acupuncture, and received daily physician consultation; MT2 patients were treated with Mokhuri Chuna and acupuncture without any herbal medication, and received daily physician consultation; and CMT patients received conventional pain management therapy that included epidural steroid injection, oral NSAID, and muscle relaxant medication, along with daily physiotherapy. The primary outcome of this pilot study was safety as measured by the type and incidence of adverse events (AEs). The secondary outcome measures included VAS score for low back pain and leg pain, Oswestry Disability Index, Oxford Claudication Score (OCS), walking capacity on a 50 m flat track and treadmill, and EuroQol-5D score. Magnetic resonance imaging was also performed up to 6 months after treatment cessation. Results: Thirty-four treated patients were included in the analysis, based on the modified intention-to-treat principle. No serious AEs were observed or reported. Compared to the CMT group, the MT1 and MT2 groups did show significant improvement at 3 and 6 months in various domains, including pain (VAS score for leg and back pain) and function (OCS and treadmill walking). Conclusion: These novel multimodal integrative treatments for LSS are both clinically safe and logistically feasible. Larger, adequately powered randomized controlled trials will be necessary to assess comparative efficacy and thoroughly analyze the cost-effectiveness of each treatment approach. Clinical trial registration number (CRIS): KCT0001218. Keywords: lumbar spinal stenosis, complementary and alternative medicine, acupuncture, Chuna, epidural steroid injection, low back pain

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

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

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

Hyeon-Kyoung Koo,1 Sung-Woo Park,2 Jeong-Woong Park,3 Hye Sook Choi,4 Tae-Hyung Kim,5 Hyoung Kyu Yoon,6 Kwang Ha Yoo,7 Ki-Suck Jung,8 Deog Kyeom Kim9 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Republic of Korea; 2Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soon Chun Hyang University Bucheon Hospital, Bucheon, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Gachon University, Gil Medical Center, Incheon, Republic of Korea; 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; 5Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 6Department of Internal Medicine, The Catholic University of Korea, Yeouido St Mary’s Hospital, Seoul, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 8Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 9Division 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 purpose: Chronic cough can be a dominant symptom of chronic obstructive pulmonary disease (COPD), although its clinical impact remains unclear. The aim of our study was to identify phenotypic differences according to the presence of chronic cough or sputum and evaluate the impact of chronic cough on the risk of acute exacerbation of COPD (AECOPD). Methods: In a nationwide COPD cohort including 1,613 COPD patients, patients with chronic cough only, those with sputum only, those with chronic bronchitis (CB), and those without cough and sputum were compared with regard to dyspnea, lung function, quality of life (QoL), and risk of AECOPD. Results: The rates of chronic cough, chronic sputum, and both were 23.4%, 32.4%, and 18.2%, respectively. Compared with patients without chronic cough, those with chronic cough exhibited a lower forced expiratory volume in 1 second (% predicted) and diffusing capacity of the lungs for carbon monoxide (% predicted), more frequent AECOPD, more severe dyspnea, and worse QoL. Pulmonary function, dyspnea severity, and QoL worsened in the following order: without cough or sputum, with sputum only, with cough only, and with CB. Multivariate analyses revealed chronic cough as an independent risk factor for a lower lung function, more severe dyspnea, and a poor QoL. Moreover, the risk of future AECOPD was significantly associated with chronic cough (odds ratio 1.56, 95% CI 1.08–2.24), but not with chronic sputum. Conclusion: Our results suggest that chronic cough should be considered as an important phenotype during the determination of high-risk groups of COPD patients. Keywords: pulmonary disease, chronic obstructive, cough, exacerbation, severity

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

Tae Hoon Kim, Jae Seung Lee, Sei Won Lee, Yeon-Mok Oh Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Abstract: Postoperative pulmonary complications (PPCs) are one of the most important causes of postoperative morbidity and mortality after abdominal surgery. Although chronic obstructive pulmonary disease (COPD) has been considered a risk factor for PPCs, it remains unclear whether mild-to-moderate COPD is a risk factor. This retrospective cohort study included 387 subjects who underwent abdominal surgery with general anesthesia in a tertiary referral hospital. PPCs included pneumonia, pulmonary edema, pulmonary thromboembolism, atelectasis, and acute exacerbation of COPD. Among the 387 subjects, PPCs developed in 14 (12.0%) of 117 patients with mild-to-moderate COPD and in 13 (15.1%) of 86 control patients. Multiple logistic regression analysis revealed that mild-to-moderate COPD was not a significant risk factor for PPCs (odds ratio [OR] =0.79; 95% confidence interval [CI] =0.31–2.03; P=0.628). However, previous hospitalization for respiratory problems (OR =4.20; 95% CI =1.52–11.59), emergency surgery (OR =3.93; 95% CI =1.75–8.82), increased amount of red blood cell (RBC) transfusion (OR =1.09; 95% CI =1.05–1.14 for one pack increase of RBC transfusion), and laparoscopic surgery (OR =0.41; 95% CI =0.18–0.93) were independent predictors of PPCs. These findings suggested that mild-to-moderate COPD may not be a significant risk factor for PPCs after abdominal surgery.Keywords: postoperative pulmonary complications, spirometry, risk factor, abdominal surgery, postoperative complications, postoperative care

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

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

Joohae Kim,1 Ho Il Yoon,2 Yeon-Mok Oh,3 Seong Yong Lim,4 Ji-Hyun Lee,5 Tae-Hyung Kim,6 Sang Yeub Lee,7 Jin Hwa Lee,8 Sang-Do Lee,3 Chang-Hoon Lee11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 3Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 5Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, 6Division of Pulmonology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, 7Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 8Department of Internal Medicine, Ewha Womans University Mokdong Hospital, College of Medicine, Ewha Womans University, Seoul, Republic of KoreaBackground: Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.Objective: We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.Methods: Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.Results: A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (-34.4±7.9 [group A]; -26.2±9.4 [group B]; -22.7±16.0 [group C]; and -24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (-32.3±7.2 vs -25.0±6.5 mL/year) (P=0.44) and the low risk group (-31.0±6.1 vs -23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.Conclusion: There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification.Keywords: annual lung function decline, chronic obstructive pulmonary disease, GOLD 2014

Miri Baek,1,* Hae-Eun Chung,1,* Jin Yu,1,* Jung-A Lee,1 Tae-Hyun Kim,2 Jae-Min Oh,2 Won-Jae Lee,3 Seung-Min Paek,3 Jong Kwon Lee,4 Jayoung Jeong, 4 Jin-Ho Choy,5 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women's University, Seoul, 2Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Gangwondo; 3Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, Taegu, 4Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk-do, 5Center for Intelligent Nano-Bio Materials, Department of Bioinspired Science and Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea*These authors contributed equally to this workBackground: This study explored the pharmacokinetics, tissue distribution, and excretion profile of zinc oxide (ZnO) nanoparticles with respect to their particle size in rats.Methods: Two ZnO nanoparticles of different size (20 nm and 70 nm) were orally administered to male and female rats, respectively. The area under the plasma concentration-time curve, tissue distribution, excretion, and the fate of the nanoparticles in organs were analyzed.Results: The plasma zinc concentration of both sizes of ZnO nanoparticles increased during the 24 hours after administration in a dose-dependent manner. They were mainly distributed to organs such as the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender. Elimination kinetics showed that a small amount of ZnO nanoparticles was excreted via the urine, while most of nanoparticles were excreted via the feces. Transmission electron microscopy and x-ray absorption spectroscopy studies in the tissues showed no noticeable ZnO nanoparticles, while new Zn-S bonds were observed in tissues.Conclusion: ZnO nanoparticles of different size were not easily absorbed into the bloodstream via the gastrointestinal tract after a single oral dose. The liver, lung, and kidney could be possible target organs for accumulation and toxicity of ZnO nanoparticles was independent of particle size or gender. ZnO nanoparticles appear to be absorbed in the organs in an ionic form rather than in a particulate form due to newly formed Zn-S bonds. The nanoparticles were mainly excreted via the feces, and smaller particles were cleared more rapidly than the larger ones. ZnO nanoparticles at a concentration below 300 mg/kg were distributed in tissues and excreted within 24 hours. These findings provide crucial information on possible acute and chronic toxicity of ZnO nanoparticles in potential target organs.Keywords: ZnO nanoparticles, pharmacokinetics, tissue distribution, excretion, fate

Tae-Ho Kim1*, Young-Il Jeong2*, Shu-Guang Jin2, Jian Pei2, Tae-Young Jung1, Kyung-Sub Moon1, In-Young Kim1, Sam-Suk Kang1, Shin Jung1,21Department of Neurosurgery, 2Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea *These authors contributed equally to this work. Background: Celecoxib, a cyclo-oxygenase (COX)-2 inhibitor, has been reported to mediate growth inhibitory effects and to induce apoptosis in various cancer cell lines. In this study, we examined the potential effects of celecoxib on glioma cell proliferation, migration, and inhibition of COX-2 expression in vitro. Methods: Celecoxib was incorporated into poly DL-lactide-co-glycolide (PLGA) nanoparticles for antitumor drug delivery. Results: PLGA nanoparticles incorporating celecoxib had spherical shapes and their particle sizes were in the range of 50–200 nm. Drug-loading efficiency was not significantly changed according to the solvent used, except for acetone. Celecoxib was released from the PLGA nanoparticles for more than 2 days, and the higher the drug content, the longer the duration of drug release. PLGA nanoparticles incorporating celecoxib showed cytotoxicity against U87MG tumor cells similar to that of celecoxib administered alone. Furthermore, celecoxib did not affect the degree of migration of U87MG cells. PLGA nanoparticles incorporating celecoxib showed dose-dependent cytotoxicity similar to that of celecoxib alone in C6 rat glioma cells. Western blot assay of the C6 cells showed that neither celecoxib alone nor PLGA nanoparticles incorporating celecoxib affected COX-2 expression. Conclusion: PLGA nanoparticles incorporating celecoxib had antitumor activity similar to that of celecoxib alone, even though these particles did not affect the degree of migration or COX-2 expression in the tumor cells. Keywords: celecoxib, cyclo-oxygenase-2, PLGA nanoparticles, glioma, antitumor activity