Search

Although several physiological effects of Chrysanthemum indicum Linne (CL) have been researched, the specific effect and molecular mechanism of CL as a functional food material for skin health remain still unknown. Here, it was observed that the α-MSH and IBMX-initiated B16F10 melanogenesis was suppressed by the CL water extract (CLE) treatment. The CLE treatment also increased the mRNA expression levels of pro-collagen1α2, collagen1α2, and fibronectin via exerting the TGF-β/JNK signaling pathway. Together, the beneficial role of CLE in skin health was demonstrated through the downregulation of melanogenesis and enhancement of skin fibril-related genes. It was also revealed that the function of CLE is mediated with the activation of the TGF-β/JNK signaling pathway. These results may provide evidences for the development of functional foods using CLE for maintaining healthy skin.

Background/aims Inhaled corticosteroids (ICS) are a treatment of choice for eosinophilic airway diseases, but their efficacy for other causes of chronic cough is controversial. Methods We conducted a prospective observational study to determine the ICS efficacy and clinical predictors of response to ICS in patients with upper airway cough syndrome (UACS) or unexplained chronic cough (UCC). Sixty-eight patients with UACS and 33 patients with UCC (duration of cough ≥ 8 weeks) were treated with ICS: 250 µg of fluticasone propionate or 400 µg of budesonide twice a day at physician's discretion. They were followed after 2 weeks to assess persistent cough which was measured as 0% to 100% compared with baseline cough frequency. Results The median grade of persistent cough after 2-week ICS treatment was 40% (interquartile range [IQR], 10 to 70) in UACS and was 50% (IQR, 20 to 70) in UCC. The only adverse event was infrequent, mild hoarse voice (five UACS and one UCC). Long duration of cough (≥ 52 weeks) and cough not aggravated by cold air exposure were predictors of a poorer response to short course ICS treatment (logistic regression analysis, p = 0.018 and p = 0.031, respectively). However, prolonged treatment with ICS more than 2 weeks was more effective in patients with long cough duration (≥ 52 weeks). Conclusion Short course ICS treatment has modest efficacy on UACS and UCC without significant adverse events. Duration of cough and cough triggered by cold air exposure were the clinical factors associated with ICS response. Extended treatment with ICS may be beneficial in patients with long duration of cough.

ALK-positive (ALK+) lung adenocarcinoma usually shows a more advanced-staged disease with frequent nodal metastasis and highly aggressive outcomes compared with EGFR-mutated lung cancers. The aim of this study was to investigate the expression profiles of several mucins in ALK + lung cancers to gain insight into the relationship between the more aggressive biological nature of ALK + lung cancers and the role of mucins. We examined the immunohistochemical profiles of mucins MUC1, MUC2, MUC5AC, and MUC6 in 19 ALK + lung cancers compared with 42 EGFR-mutated lung cancers. ALK + cancers were found to occur in younger patients and were characterized by a solid-predominant histologic subtype with frequent signet ring cells and peritumoral muciphages. By contrast, EGFR-mutated cancers lacked ALK-specific histological patterns. Although all MUC1 and MUC5AC were expressed in both subtypes, MUC1 expression in ALK + cancers was visualized exclusively through cytoplasmic staining, whereas those in EGFR-mutated cancers were predominantly membranous staining in apical area (92.9%) and focally in cytoplasmic staining (7.1%). MUC5AC expression in ALK + cancers was exclusively visualized through cytoplasmic staining (100%), whereas EGFR-mutated cancers showed predominantly perinuclear dot-like patterns (90.5%) and focal cytoplasmic staining (9.5%). MUC2 and MUC6 expression was not detected in either type of lung cancer. Conclusions The high frequency of both MUC1 and MUC5AC cytoplasmic expression, coupled with a lack of MUC2 and MUC6 expression in ALK + lung cancer may contribute to the biologically aggressive behavior of ALK + cancer. Inhibitors to these types of mucins may thus act as a barrier to cancerous extension reducing their aggressive behavior.

Background/Aims The relationship between nonpulmonary organ failure and the development of acute respiratory distress syndrome (ARDS) in patients with sepsis has not been well studied. Methods We retrospectively reviewed the medical records of patients with septic bacteremia admitted to the medical intensive care unit (ICU) of a tertiary academic hospital between January 2013 and December 2016. Results The study enrolled 125 patients of median age 73.0 years. Urinary (n = 47), hepatobiliary (n = 30), and pulmonary infections (n = 28) were the most common causes of sepsis; the incidence of ARDS was 17.6%. The total number of nonpulmonary organ failures at the time of ICU admission was higher in patients with ARDS than in those without (p = 0.011), and the cardiovascular, central nervous system (CNS), and coagulation scores were significantly higher in ARDS patients. On multivariate analysis, apart from pneumonia sepsis, the CNS (odds ratio [OR], 1.917; 95% confidence interval [CI], 1.097 to 3.348) and coagulation scores (OR, 2.669; 95% CI, 1.438 to 4.954) were significantly associated with ARDS development. The 28-day and in-hospital mortality rates were higher in those with ARDS than in those without (63.6 vs. 8.7%, p < 0.001; 72.7% vs. 11.7%, p < 0.001), and ARDS development was found to be an independent risk factor for 28-day mortality. Conclusions Apart from pneumonia, CNS dysfunction and coagulopathy were significantly associated with ARDS development, which was an independent risk factor for 28-day mortality.

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

Background Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. Methods This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. Results The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. Conclusion This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.

Background: The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD). Objective: The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms. Methods: We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of Results: After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference –4.7 [95% CI –7.9 to –1.6] and –4.8 [95% CI –7.9 to –1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference –5.0 [95% CI –8.6 to –1.4]) compared to no regular treatment at 12 months of follow-up. Conclusions: Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

Background: A single long-acting bronchodilator, ultra-long acting muscarinic antagonist (ultra-LAMA) or ultra-long acting β2-agonist (ultra-LABA) is preferred for the initial treatment of patients with chronic obstructive pulmonary disease (COPD); however, there are few head-to-head comparative studies between the two. Here, a meta-analysis of randomized controlled trials was performed to compare the clinical efficacy between ultra-LABA and ultra-LAMA in patients with moderate-to-severe COPD. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched (to March 1, 2017) to identify all published randomized controlled trials. Results: Of the 12,906 articles found by searching the databases, we obtained data from 10,591 patients with COPD (LABA, n=5,058; LAMA, n=5,533) in seven published studies. Our results showed that COPD exacerbation were significantly lower in patients taking ultra-LAMA than those taking ultra-LABA (odds ratio =0.857, P=0.0008). However, no significant differences were observed between ultra-LAMA and ultra-LABA patients regarding improvement in trough forced expiratory volume in 1 s, the transitional dyspnea index, or St. George’s Respiratory Questionnaire score. Conclusions: This study suggests that COPD exacerbation occurred less often in patients taking an ultra-LAMA than in those taking an ultra-LABA with similar efficacy of lung function and quality of life.

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterized by the overlapping clinical features of asthma and COPD. To evaluate the appropriateness of different sets of ACO definition, we compared the clinical characteristics of the previously defined diagnostic criteria and the specialist opinion in this study. Methods: Patients enrolled in the KOrea COpd Subgroup Study (KOCOSS) were evaluated. Based on the questionnaire data, the patients were categorized into the ACO and non-ACO COPD groups according to the four sets of the diagnostic criteria. Results: In total 1,475 patients evaluated: 202 of 1,475 (13.6%), 32 of 1,475 (2.2%), 178 of 1,113 (16.0%), and 305 of 1,250 (24.4%) were categorized as ACO according to the modified Spanish Society of Pneumonology and Thoracic Surgery (SEPAR), American Thoracic Society (ATS) Roundtable, Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and the specialists diagnosis, respectively. The ACO group defined according to the GINA/GOLD criteria showed significantly higher St. George''s Respiratory Questionnaire and COPD Assessment Test scores than the non-ACO COPD group. When the modified SEPAR definition was applied, the ACO group showed a significantly larger decrease in the forced expiratory volume in 1 second (FEV1, %). The ACO group defined by the ATS Roundtable showed significantly larger decrease in the forced vital capacity values compared to the non-ACO COPD group (-18.9% vs. -2.2%, p=0.007 and -412 mL vs. -17 mL, p=0.036). The ACO group diagnosed by the specialists showed a significantly larger decrease in the FEV1 (%) compared to the non-ACO group (-5.4% vs. -0.2%, p=0.003). Conclusion: In this study, the prevalence and clinical characteristics of ACO varied depending on the diagnostic criteria applied. With the criteria which are relatively easy to use, defining ACO by the specialists diagnosis may be more practical in clinical applications.

Background Statins, which are a type of 3-hydroxy-3-methylglutaryl-CoA inhibitor, have multiple therapeutic effects, including anti-inflammatory and immunomodulatory properties. Despite positive preclinical data on statin use in patients with asthma, clinical trials and epidemiological studies have yielded conflicting results. Objective To evaluate the association between statin use and an asthma diagnosis in all participants and the effects of statins on asthma-related outcomes among patients with asthma using a national health screening cohort. Methods Patients with asthma and control participants matched for age group, sex, income, and region of residence were selected from the Korean National Health Insurance Service-Health Screening Cohort data. This case-control study comprised 88,780 people with asthma and the same number of control participants. Asthma exacerbation (AE) was defined as an emergency department visit, a history of hospitalization due to asthma, or the use of systemic steroids for 2 weeks. Conditional and unconditional logistic regression analyses were used to evaluate the effect of the previous use of statins on an asthma diagnosis or AE after adjusting for multiple covariates. Results A significant association between a statin prescription and an asthma diagnosis was not observed in this cohort (adjusted odds ratio, 1.01; 95% CI, 0.98-1.03; P = .633 for 1 year of statin prescription). Among the patients with asthma, 16.54% (n = 14,687) were categorized into the AE group and the others (n = 74,093) were categorized into the no AE group. A statin prescription was associated with fewer AEs in patients with asthma (adjusted odds ratio, 0.89; 95% CI, 0.84-0.93; P Conclusions Statin use was associated with a reduced risk of asthma-related emergency department visits, hospitalizations, and systemic steroid use in patients with asthma in this cohort study.

Background The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise. Methods The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed. Results A total of 612 patients were diagnosed with lung cancer from February through June, 2017–2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III–IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same. Conclusions The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.

Background: Since complete blood count (CBC) can be easily and repeatedly measured at the usual clinical setting, the various CBC biomarkers including eosinophil count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and eosinophil-basophil ratio have been studied for COPD. Recently, the roles of eosinophil-platelet interactions were emphasized from in vitro or animal model studies. Here, we extensively evaluated the impacts of CBC profiles including eosinophil-platelet interaction on clinical outcomes of stable COPD in Korean cohorts. Methods: The COPD patients enrolled in Korean COPD Subtype Study (KOCOSS) or Seoul National University Airway Registry between 2011 and 2018 were analyzed. Based on the CBC profiles at the time of enrollment, their association with the rate of acute exacerbation (AE) within one year and the annual decline rate of forced expiratory volume in 1 second (FEV1) were evaluated by using negative binomial regression model and linear mixed-effects model. Results: Among 2,221 COPD patients, 1,202 patients were analyzed. Multivariate analysis showed that baseline FEV1 is the most significant factor for both AE rate and FEV1 decline rate. High EBR is associated with high moderate-to-severe AE rates, and both EBR and NLR were related to severe AE rates in addition to FEV1 and the history of AE events. The patients with low eosinophil counts tended faster FEV1 decline, however, platelet counts or eosinophil-platelet interaction terms were not significant factors for outcomes. Conclusion: EBR and NLR are independent prognostic markers for the moderate-to-severe AE and FEV1 decline rate of stable COPD, while eosinophil-platelet interaction had a limited role in predicting clinical outcomes.

Supplemental Digital Content is available in the text, There are limited data regarding the association between brain natriuretic peptide (BNP) levels obtained after weaning from extracorporeal membrane oxygenation (ECMO) and the outcomes of patients with acute coronary syndrome (ACS)-associated cardiogenic shock. We prospectively obtained data regarding patients (aged ≥ 19 years) with ACS-associated cardiogenic shock who received ECMO and were subsequently weaned off the treatment. BNP levels were collected at 5 time points: pre-ECMO implantation, post-ECMO implantation, pre-ECMO weaning, day 1 after ECMO weaning, and day 5 after ECMO weaning. Of 48 patients with ACS-related cardiogenic shock, 33 were included in this analysis. Mean patient age was 59.0 (50.0–66.5) years, and 5 patients (15.2%) were women. Eight patients had asystole/pulseless electrical activity before ECMO and 14 (42.4%) had 3-vessel disease on coronary angiography. During the 6-month follow up, 12 (36.4%) patients died. BNP levels after ECMO weaning were significantly different between 6-month survivors and non-survivors. Cox proportional hazards model revealed that BNP levels (tertiles) on days 1 and 5 after ECMO weaning were significantly associated with 6-month mortality (hazard ratio, 7.872; 95% confidence interval, 1.870–32.756; 8.658 and 1.904–39.365, respectively). According to the Kaplan–Meier curves, the first tertile had significantly longer survival compared to the third tertile for both days 1 and 5 after ECMO weaning. Post-ECMO weaning BNP levels (days 1 and 5) were significantly associated with increased 6-month mortality in patients with ACS complicated by refractory cardiogenic shock who were weaned off ECMO.

PURPOSE Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. METHODS The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. RESULTS Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. CONCLUSIONS TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Background Long-term oxygen therapy provides various benefits, including prolonged survival for severely hypoxic chronic obstructive pulmonary disease (COPD) patients. However, adequate management strategies for home oxygen therapy are not well established in Korea. This study aimed to explore the current situation of home oxygen therapy to provide basic data for developing a strategy for COPD patients on home oxygen therapy. Methods In this cross-sectional study, we enrolled COPD patients using home oxygen therapy for at least 1 month. Face-to-face interviews were conducted, guided by a structured questionnaire about home oxygen therapy. Results A total of 195 patients were enrolled. The mean age was 72.6 ± 9.7 years, and 76.4% of patients were men. The mean modified Medical Research Council, COPD Assessment Test, and EuroQol-5D index scores were 3.4 ± 0.8, 29.7 ± 6.8, and 0.35 ± 0.44, respectively. At rest, patients were prescribed oxygen for 12.5 ± 7.3 hr/day and used 12.9 ± 8.5 hr/day on average. During exercise, the mean duration of prescribed oxygen was 6.6 ± 4.3 hr/day, and the actual use was 1.1 ± 2.9 hr/day. A total of 25.6% of patients used ambulatory oxygen; with financial burden the main reason for nonuse. The mean number of hospitalizations and emergency room visits were 2.5 and 2.6, respectively. Conclusion This study revealed low adherence to home oxygen therapy, poor health-related quality of life, frequent hospitalizations, and a high financial burden among COPD patients using home oxygen therapy. The study highlights the need for adequate strategies to improve the quality of home oxygen therapy., Graphical Abstract

Objectives: Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma–COPD overlap (ACO). We assessed the effect of ICS treatment on patients with ACO using five sets of diagnostic criteria to identify predictors of the response. Methods: Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed-up for 1 year. Measurements and Main Results: Among 1,067 COPD patients, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ACO by the GINA/GOLD criteria, the ATS roundtable criteria, the modified Spanish criteria, the updated Spanish criteria, and specialists’ diagnoses, respectively. Specialists’ diagnoses were most consistent with the GINA/GOLD criteria (area under the receiver operating characteristic curve = 0.87). According to the specialists’ diagnoses, the ACO exacerbation rate was higher than that for COPD alone (incidence rate ratio [IRR] = 1.65; p Conclusions: This study suggests that ICS treatment can decrease the risk of exacerbation in patients with ACO, and that a blood eosinophil count of ≥300 cells/µL can predict the response to ICS treatment.

Background Pulmonary functions are interpreted using predicted values from reference equations that vary with ethnicity, gender, age, height, and weight. The universally used Choi's reference equations are not validated for Korean populations, and the purpose of this study was to validate them and develop new reference equations. Methods Subjects with normal spirometry and chest radiographs, no co-morbidities, and non-smokers, from the Korean National Health and National Examination Survey (KNHANES)-VI were enrolled (n = 117). Intraclass correlation coefficient (ICC) was assessed for reliability of reference equations. New reference equations were developed using linear regression analysis. Differences between observed and predicted values were assessed to compare the reference equations from Choi's, Global Lung Function Initiative 2012, KNHANES-IV, and newly developed equations. Results The ICC of Choi's reference equations was 0.854 (P < 0.001). The new reference equations for men were: forced vital capacity (FVC) (L) = − 4.38775 − 0.01184 × age + 0.05547 × height, forced expiratory volume – 1 second (FEV1) (L) = − 2.40147 − 0.02134 × age + 0.04103 × height; and for women: FVC (L) = − 3.09063 + 0.003904 × age + 0.038694 × height; FEV1 (L) = − 1.32933 − 0.00872 × age + 0.02762 × height. The differences between the predicted and observed means were largest in Choi's equations, but lowest in the new equations with highest goodness of fit. Conclusion Because Choi's reference equations presented larger differences from the observed values, despite reliability, and the new reference equations showed better goodness of fit, we suggest the latter for Korean populations., Graphical Abstract

Although several physiological effects of Chrysanthemum indicum Linné (CL) have been researched, the specific effect and molecular mechanism of CL as a functional food material for skin health remain still unknown. Here, it was observed that the α-MSH and IBMX-initiated B16F10 melanogenesis was suppressed by the CL water extract (CLE) treatment. The CLE treatment also increased the mRNA expression levels of pro-collagen1α2, collagen1α2, and fibronectin via exerting the TGF-β/JNK signaling pathway. Together, the beneficial role of CLE in skin health was demonstrated through the downregulation of melanogenesis and enhancement of skin fibril-related genes. It was also revealed that the function of CLE is mediated with the activation of the TGF-β/JNK signaling pathway. These results may provide evidences for the development of functional foods using CLE for maintaining healthy skin.

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

Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients with chronic airway diseases is controversial. We conducted a retrospective study to characterize the clinical features of IgGSCD in this population. This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively). The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036). In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis., Graphical Abstract

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies., Graphical Abstract

We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment.To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin.A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups.Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001).The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of DIC at day 1 (

Levodropropizine is commonly used as an antitussive drug for acute and chronic cough. It is a non-opioid agent with peripheral antitussive action via the modulation of sensory neuropeptide levels in the airways. Thus, levodropropizine has a more tolerable profile than opioid antitussives. However, we experienced 3 cases of levodropropizine-induced anaphylaxis. Three patients commonly presented with generalized urticaria, dyspnea, and collapse after taking cold medication including levodropropizine. To find out the culprit drug, we performed skin tests, oral provocation tests (OPTs), and basophil activation tests (BATs). Two patients were confirmed as having levodropropizine-induced anaphylaxis by OPTs, and one of them showed positive to skin prick tests (SPTs). The other patient was confirmed by skin tests and BATs. When we analyzed pharmacovigilance data related to levodropropizine collected for 5 years, most cases (78.9%) had allergic reactions, such as rash, urticaria, angioedema, and anaphylaxis. Therefore, physicians should consider that levodropropizine can be a culprit drug, when anaphylaxis occurs after taking anti-cough or common cold medication.

Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).To investigate the effect of ICS treatment on patients with ACO using 5 sets of diagnostic criteria.Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed up for 1 year were included in an exacerbation analysis.Among 1067 patients with COPD, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ACO by the Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, the American Thoracic Society roundtable criteria, the modified Spanish criteria, the updated Spanish criteria, and specialists' diagnoses, respectively. According to the specialists' diagnoses, the ACO exacerbation rate was higher than that for COPD alone (incidence rate ratio [IRR] = 1.65; P.01), even after adjustment for covariates. Patients with ACO who used ICSs experienced less exacerbation, according to the specialists' diagnoses and the GINA/GOLD criteria (IRR = 0.55, P = .026; IRR = 0.69, P = .046, respectively). The only factor associated with a decrease in ACO exacerbation after ICS use was a blood eosinophil count of ≥300 cells/μL (IRR = 0.52, P = .03) irrespective of the diagnosis of ACO by any set of criteria.This study suggests that ICS treatment can decrease the risk of exacerbation in patients with ACO, and that a blood eosinophil count of ≥300 cells/μL can predict the response to ICS treatment.

Background/Aims: Many chronic obstructive pulmonary disease (COPD) patients have physical limitations. We investigated EuroQol five-dimensions five-level (EQ-5D-5L) of COPD patients to assess quality of life, and assessed indirect bur den including time expenditure to visit doctor, home care rate, and caregiver re lated burden. Methods: We recruited 355 COPD patients according to severity of airflow limita tion that severity was set at 10% mild, 40% moderate, 30% severe, and 20% very severe in two primary and 11 secondary/tertiary hospitals. Eligible patients were aged ≥ 40 years, who have been diagnosed with COPD for more than 1 year. Pa tients were recruited between June 2015 and October 2016. Results: The quality of life tended to decline with age, from mild to very severe impairment, as revealed by the EQ-5D-5L scores and the EQ visual analog scale. Family caregivers accompanied 22.6% of patients who visited outpatient clinics, and 25% of stage IV COPD patients. During emergency visits and hospitalization, this figure increased to > 60%. The home care rates were 28.5% for stage I pa tients, and 34.4, 31.8, and 52% for stage II to IV patients, respectively. The percent age of caregivers who stopped working was 13.6%. The EQ-5D index was strongly associated with the dyspnea scale (r = -0.64, p < 0.001). The average required time to see a doctor and visit the pharmacy was 154 minutes. Conclusions: In patients with COPD, the EQ-5D index decreased and disease-re lated home caregiving increased with airflow limitation. We considered the care giver-related burden when making a strategy for COPD management.

Background Thyroid transcription factor (TTF)-1 expression is a diagnostic marker and a good prognostic indicator for lung adenocarcinoma. However, its good prognostic ability might be due to epidermal growth factor receptor (EGFR)-sensitizing mutations as shown by the positive correlation between TTF-1 expression and EGFR mutations. We explored the prognostic impact of TTF-1 expression according to EGFR-sensitizing mutation status in lung adenocarcinoma patients. Methods We conducted a retrospective cohort study of patients with stage IV lung adenocarcinoma. Data were extracted from the lung cancer registry of Hallym University Medical Centers (three hospitals) in Korea between March 2006 and March 2016. Results Overall, 173 patients were included. EGFR-sensitizing mutations were detected in 84 (51.4%) patients. TTF-1 expression was positive in 139 (80.3%) patients; it was significantly correlated with EGFR-sensitizing mutations (p

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

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases. Overlap in the clinical features of these 2 diseases is observed in many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been proposed. However, the definition of ACO and the clinical significance remains to be determined.We evaluated the prevalence and risk of acute exacerbation in ACO among Korean COPD patients as defined by modified Spanish criteria and American Thoracic Society (ATS) Roundtable criteria.The prevalence of ACO was 47.7% (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable criteria. ACO, regardless of criteria, did not significant affect the exacerbation risk during at least 1-year follow-up period.Substantial discrepancies were found in the prevalence and outcome of ACO according to different diagnostic criteria, which would compromise implementation of ACO before the definition is established.

Background/Aims: Cigarette smoking is the most common risk factor for chronic obstructive pulmonary disease (COPD). However, few studies of the attitudes toward COPD of smokers, the group at risk of developing this condition, have been conducted. The purpose of this study was to explore the awareness of and attitudes toward COPD of current smokers. Methods: The sample consisted of 502 individuals aged 45 and older from throughout Korea who smoked at least 10 packs of cigarettes per year. Telephone interviews using a structured questionnaire were conducted with respondents. Results: First, we evaluated the health status of subjects, finding that 45.4% considered themselves to be in good health. We also asked about COPD-related symptoms, and 60.6% of subjects reported such symptoms. However, only 1.2% of subjects had been diagnosed with or treated for COPD, only 0.4% spontaneously mentioned COPD as a respiratory disease, and only 26.5% recognized COPD as a respiratory disease after seeing a list of such diseases. Television ranked as the top source of information about COPD. The willingness of 45.0% of subjects to stop smoking increased after being informed about COPD. Conclusions: Despite having COPD-related symptoms, most smokers did not know that COPD is a respiratory disease. The attitudes of smokers toward COPD and smoking cessation varied according to socioeconomic status. In summary, a continuous effort to increase the awareness of COPD among smokers is needed. Additionally, strategies tailored according to different socioeconomic groups will also be necessary.

Background: A well-organized education program improved the patients’ knowledge about their disease, inhaler technique and quality of life in asthma and chronic obstructive pulmonary disease (COPD) patients. The effectiveness of the education program can be evaluated by assessing patients’ satisfaction with the education program as well. In this study, we compared the patients’ satisfaction with education program between COPD and asthma patients. Methods: A total of 284 asthma and COPD patients were enrolled. Three educational visits were conducted at 2-week intervals. On the first visit, we taught the patients about their diseases and the proper inhaler technique. On the second visit, non-pharmacologic treatments and action plans for acute exacerbation were introduced. On the final appointment, we summarized the educational concepts covered in the two prior visits. After the education program, the patients were assessed for their quality of life, knowledge of chronic airways disease, and satisfaction with the education program, using a structured questionnaire. Results: After the education program, 99.3% of the asthma patients knew much more about their disease and 96.8% agreed that education from the hospital is needed. For COPD patients, 94.8% felt more informed about their disease and 95.7% agreed that education from the hospital is needed. However, 17.1% of asthma patients and 13.5% of COPD patients disagreed to paying an additional fee for the education program. Finally, the knowledge improvement was linked to patient satisfaction with the education program. Conclusions: The improvement in self-knowledge about their disease was linked to their satisfaction with the education program. However, costs associated with the program could limit its accessibility to the patients. The patient education program is a self-management intervention to improve the lives of patients with asthma and COPD. Thus, a policy to reduce the economic burden of the patients should be considered to disseminate the education program in primary care clinics.

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

BACKGROUND: The role of extended-spectrum beta-lactamase (ESBL)-producing or multidrug-resistant (MDR) organisms in patients with sepsis secondary to urinary traction infection (UTI) has not been investigated extensively in the intensive care unit (ICU) setting. METHODS: Patients with UTI sepsis admitted to the ICU were retrospectively enrolled in this study (January 2009-December 2012). We investigated the impact of ESBL-producing and ESBL-negative MDR organisms on hospital outcome. RESULTS: In total, 94 patients were enrolled (median age, 73.0 years; female, 81.9%), and ESBL-producing and ESBL-negative MDR organisms accounted for 20.2% (n = 19) and 30.9% (n = 29), respectively. Both patients with ESBL-producing and ESBL-negative MDR organisms were more likely to experience a delay in adequate antibiotic therapy than those with non-ESBL/non-MDR organisms (p < 0.001 and p = 0.032, respectively). However, only patients with ESBL-producing organisms showed a higher mortality rate (ESBL vs. ESBL-negative MDR vs. non-ESBL/non-MDR, 31.6% vs. 10.3%.vs. 10.9%, respectively). In multivariate analyses, ESBL production was significantly associated with hospital mortality (odds ratio, 11.547; 95micro confidence interval, 1.047-127.373), and prior admission was a significant predictor of ESBL production. CONCLUSIONS: Although both ESBL-producing and ESBL-negative MDR organisms are associated with delayed administration of appropriate antibiotics, only ESBL production is a significant predictor of hospital mortality among patients with UTI sepsis in the ICU setting.

Supplemental Digital Content is available in the text, The early detection and diagnosis of chronic obstructive pulmonary disease (COPD) is critical to providing appropriate and timely treatment. We explored a new active case-finding strategy for COPD using handheld spirometry. We recruited subjects over 40 years of age with a smoking history of more than 10 pack-years who visited a primary clinic complaining of respiratory symptoms. A total of 190 of subjects were enrolled. Medical information was obtained from historical records and physical examination by general practitioners. All subjects had their pulmonary function evaluated using handheld spirometry with a COPD-6 device. Because forced expiratory volume in 6 seconds (FEV6) has been suggested as an alternative to FVC, we measured forced expiratory volume in 1 second (FEV1)/FEV6 for diagnosis of airflow limitation. All subjects were then referred to tertiary referral hospitals to complete a “Could it be COPD?” questionnaire, handheld spiromtery, and conventional spirometry. The results of each instrument were compared to evaluate the efficacy of both handheld spirometry and the questionnaire. COPD was newly diagnosed in 45 (23.7%) patients. According to our receiver-operating characteristic (ROC) curve analysis, sensitivity and specificity were maximal when the FEV1/FEV6 ratio was less than 77%. The area under the ROC curve was 0.759. The sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 77.1%, 50%, and 90%, respectively. The area under the ROC curve of respiratory symptoms listed on the questionnaire ranged from 0.5 to 0.65, which indicates that there is almost no difference compared with the results of handheld spirometry. The present study demonstrated the efficacy of handheld spirometry as an active case-finding tool for COPD in a primary clinical setting. This study suggested that physicians should recommend handheld spirometry for people over the age of 40, who have a smoking history of more than 10 pack-years, regardless of respiratory symptoms. Furthermore, people who have abnormal results, determined using the FEV1/FEV6 ≤0.77 cut-off, should be referred for further conventional spirometry to confirm the diagnosis of COPD. However, further studies within the general population are necessary to establish efficacy in the public.

Background Patients with asthma often suffer from depression and vice versa. However, the temporal relationship between the 2 diseases has remained elusive. Objective The aim of this study was to determine the bidirectional relationship between asthma and depression in adults, using national cohort samples in Korea. Methods Using the national cohort from the study by the Korean Health Insurance Review and Assessment Service, patients with asthma and control participants were selected and matched by age group, sex, income group, region of residence, and medical histories. A stratified Cox proportional hazards model was used to analyze the hazard ratio (HR) of asthma with depression (study 1) and depression with asthma (study 2). Results In study 1, the HR of depressive disorders was significantly higher in patients with asthma than in patients without asthma (HR, 1.35; 95% CI, 1.31-1.40). In study 2, the HR of asthma in patients with depression was significantly higher than that in patients without depression (HR, 1.25; 95% CI, 1.21-1.29). Conclusion A bidirectional association between asthma and depression was observed in this study.

Background: Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. Methods: This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. Results: The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. Conclusion: This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.

Previous studies reported that the most common chronic condition found among hospitalized patients due to the novel 2009 H1N1 influenza was asthma. However, these studies did not include a concurrent control group. Thus, we investigated the association of asthma status and severity of H1N1 influenza in adults.The study was designed as a multi-site case-control study. Cases were patients who had positive PCR for H1N1 influenza and were admitted to the ICU or general ward with a diagnosis of H1N1 influenza from 1 January 2009 to 31 December 2009. Controls were patients who had positive PCR for H1N1 influenza, but were not admitted to hospitals.There were 91 H1N1 cases admitted to either ICU (n = 41) or general hospital ward (n = 50), and 56 controls who met the matching criteria were available. Of the 91 cases, the mean age was 47.3 years, 59% were female, and 38% had comorbid conditions. Of the 91 cases, 12 (13%) had asthma. Stratified analysis by comorbid conditions showed that among those without any comorbid conditions, 8 of 56 cases (14%) and 2 of 49 controls (4%) had asthma, (OR: 3.92, 95% CI: 0.79-19.42, p = 0.095) whereas, among the 39 subjects with one or more comorbid conditions, one of 7 controls (14%) had asthma and 4 of 35 (11%) cases had asthma (p = 0.83).Asthma may be associated with severity of H1N1 influenza among those without any non-asthma comorbid conditions. However, the limited sample size did not allow this study to fully establish statistical significance. We still recommend asthmatics as a priority group for influenza vaccination and treatment.

Background: Inhaled corticosteroids (ICS) are the drug of choice for eosinophilic airway diseases, but their efficacy on other causes of chronic cough is controversial. Aims and objectives: This was a prospective observational study to find out ICS efficacy and clinical predictors of response in patients with upper airway cough syndrome (UACS) and idiopathic chronic cough (ICC). Methods: Patients (≥18 year-old) with UACS or ICC (duration of cough ≥ 8 weeks) were included. Patients with asthma or frequent gastro-esophageal reflux symptoms were excluded. They were treated with ICS: 250µg of fluticasone propionate or 400µg of budesonide twice a day at physician9s discretion. Any other respiratory medicine was prohibited. Baseline cough frequency and severity were scored 1-4. They were followed after 2 weeks to assess remnant cough which was measured as 0-100% compared with baseline cough level. Results: One hundred thirty two patients were enrolled (90 UACS, 42 ICC) and 101/132 (76.5%) were successfully followed (mean follow up visit, 15.3 ± 4.0 day). The mean remnant cough were 43.5 ± 33.6 in UACS patients and 46.3 ± 33.8 in ICC patients (p=0.685). Among clinical factors such as cause of cough, cough aggravation by cold air exposure, nocturnal awakening by cough, duration of cough, smoking status, sex, cough frequency and severity, multivariate analysis revealed duration of cough was only the predictor of ICS response. Long duration of cough (≥52 weeks) was poor response predictor of short course ICS treatment (Cox regression analysis, p=0.018). Conclusion: ICS treatment had modest efficacy on UACS and ICC. Long duration of cough was a bad response predictor of short course ICS treatment.

Background: Cold air is a major environmental factor that exacerbates bronchial asthma. Transient receptor potential melastatin family member 8 (TRPM8) receptor is a cold- and menthol-sensing cation channel expressed in sensory neurons as well as bronchial epithelial cells. Objectives: We sought to explore the role of TRPM8 receptor expressed in bronchial epithelial cells in airway inflammation. Methods: Human airway epithelial cell line, BEAS-2B, was treated with menthol, TRPM8 antagonist (BCTC, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide) and dexamethasone in dose- and time- dependent manner. The mRNA of TRPM8 and proinflammatory cytokines such as IL-4, 6, 8, 13, 25, 33 was determined by real-time quantitative PCR. The expression of TRPM8 in bronchial epithelial cells was determined by western blotting and immunofluorescence. ELISA of TRPM8 performed using the induced sputum of asthmatics and normal controls. Results: TRPM8 protein expression was significantly increased in patients with asthma compared with healthy controls using ELISA of sputum supernatants. TRPM8 receptor was expressed primarily in bronchial epithelial cells at both mRNA and protein levels with statistical significances. Activating TRPM8 receptors by menthol was coupled with enhanced expression of the inflammatory cytokines of some IL and treatment with BCTC and dexamethasone attenuated the expression of the inflammatory cytokines. Conclusions: Activation of TRPM8 receptor of bronchial epithelial cells induces airway inflammatory cytokines, suggesting the TRPM8 receptor may involve in cold induced asthma exacerbations.

Joo Kyung Kim,1 Soo Haeng Lee,1 Bho Hyeon Lee,1 Chang Youl Lee,2 Do Jin Kim,3 Kyung Hoon Min,4 Sung Kyoung Kim,5 Kwang Ha Yoo,6 Ki-Suck Jung,1 Yong Il Hwang1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St Vincent’s Hospital, The Catholic University of Korea, Suwon, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea Introduction: COPD exacerbation negatively impacts the patient’s quality of life and lung function, increases mortality, and increases socioeconomic costs. In a real-world setting, the majority of patients with COPD have mild-to-moderate airflow limitation. Therefore, it is important to evaluate COPD exacerbation in patients with mild-to-moderate airflow limitation, although most studies have focused on the patients with moderate or severe COPD. The objective of this study was to evaluate factors associated with COPD exacerbation in patients with mild-to-moderate airflow limitation. Methods: Patients registered in the Korean COPD Subtype Study cohort were recruited from 37 tertiary referral hospitals in Korea. We obtained their clinical data including demographic characteristics, past medical history, and comorbidities from medical records. Patients were required to visit the hospital to document their COPD status using self-administered questionnaires every 6 months. Results: A total of 570 patients with mild-to-moderate airflow limitation were enrolled. During the first year of follow-up, 30.5% patients experienced acute exacerbation, with exacerbations being more common in patients with poor lung function. Assessed factors associated with COPD exacerbation included COPD assessment test scores, modified Medical Research Council dyspnea assessment test scores, St George’s Respiratory Questionnaire for COPD scores, a previous history of exacerbation, and histories of pneumonia and allergic rhinitis. Logistic regression tests revealed St George’s Respiratory Questionnaire for COPD scores (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00–1.04; P=0.034), a previous history of exacerbation (OR, 3.12; 95% CI, 1.35–7.23; P=0.008), and a history of pneumonia (OR, 1.85; 95% CI, 1.06–3.25; P=0.032) as risk factors for COPD exacerbation. Conclusion: Our results suggest that COPD exacerbation in patients with mild-to-moderate airflow limitation is associated with the patient’s quality of life, previous history of exacerbation, and history of pneumonia. Keywords: COPD, exacerbation, risk factors