Since 2015, the Health Insurance Review and Assessment Service (HIRA) has performed annual qualitative assessments of asthma management provided by all medical institutions that care for asthma patients in Korea. According to the third report of qualitative assessment of asthma management in 2017, the assessment appears to have contributed to improving the quality of asthma care provided by medical institutions, especially primary clinics. However, there is still a gap between the ideal goals of asthma management and actual health care policies/regulations in real clinical settings, which leads to the state of standstill with respect to the quality of asthma management despite considerable efforts such as the qualitative assessment of asthma management by national agencies such as the HIRA. At this point, a harmonized approach is needed to raise the level of asthma management among several components including medical policies, efforts of academic associations such as education and distribution of the guideline for management, and reliable financial support by the government.

Chronic obstructive pulmonary disease (COPD) had been considered the only major disease that is continuing to increase in prevalence. There were a few studies about the change of the prevalence of COPD, which showed the prevalence of COPD did not increase. In this review, we report on the trends in the prevalence of COPD in Korea using the data from Korea National Health and Nutrition Examination Survey (KNHANES). The prevalence of COPD in 2015 was 13.4% (male, 21.6%; female, 5.8%). The prevalence of COPD did not change much, which ranged from 13.1% to 14.6% during the period from 2010 to 2015. Among the subjects found to have COPD by spirometry, only 2.8% had been diagnosed as COPD by physicians during the period from 2011 and 2015. In conclusion, the prevalence of COPD did not change significantly during the period from 2010 to 2015. And most COPD patients still had not been diagnosed by physicians and consequently had not been treated appropriately.

Chronic obstructive pulmonary disease (COPD) results in high morbidity and mortality among patients both domestically and globally. The Korean clinical practice guideline for COPD was revised in 2014. It was drafted by the members of the Korean Academy of Tuberculosis and Respiratory Diseases, as well as participating members of the Health Insurance Review and Assessment Service, Korean Physicians' Association, and Korea Respiration Trouble Association. This revised guideline covers a wide range of topics, including the epidemiology, diagnosis, assessment, monitoring, management, exacerbation, and comorbidities of COPD in Korea. We drafted a guideline on COPD management by performing systematic reviews on the topic of management with the help of a meta-analysis expert. We expect this guideline will be helpful medical doctors treating patients with respiratory conditions, other health care professionals, and government personnel in South Korea.

Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition, and effective treatment of outpatients can prevent worsening of the illness and hospitalization. Current COPD guidelines provide appropriate guidance for the diagnosis and treatment of patients with COPD. In fact, it has been shown that when appropriate guidance and treatment are performed, the morbidity and mortality rates of COPD patients are reduced. However, there is a gap between the clinical guidelines and the actual clinical treatment. Therefore, the Health Insurance Review and Assessment Service (HIRA) conducted an evaluation of the adequacy of COPD diagnosis and treatment using the Claims Database of HIRA. This review provides a summary of the COPD adequacy assessment results reported by the HIRA and some brief comments on the results.

Background: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. Methods: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. Results: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. Conclusion: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Background:N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH) to N-acetyl INH through a process of acetylation, and confers low-level resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB, NAT2 in humans performs the same function of acetylation. Rapid acetylators, may not respond to INH treatment efficiently, and could be a potential risk factor, for the development of INH resistance in humans. Methods: To understand the contribution of NAT of MTB and NAT2 of humans in developing INH resistance using in silico approaches, in this study, the wild type (WT) and mutant (MT)-NATs of MTB, and humans, were modeled and docked, with substrates and product (acetyl CoA, INH, and acetyl INH). The MT models were built, using templates 4BGF of MTB, and 2PFR of humans. Results: On the basis of docking results of MTB-NAT, it can be suggested that in comparison to the WT, binding affinity of MT-G207R, was found to be lower with acetyl CoA, and higher with acetyl-INH and INH. In case of MT-NAT2 from humans, the pattern of score with respect to acetyl CoA and acetyl-INH, was similar to MT-NAT of MTB, but revealed a decrease in INH score. Conclusion: In MTB, MT-NAT revealed high affinity towards acetyl-INH, which can be interpreted as increased formation of acetyl-INH, and therefore, may lead to INH resistance through inactivation of INH. Similarly, in MT-NAT2 (rapid acetylators), acetylation occurs rapidly, serving as a possible risk factor for developing INH resistance in humans.

Background: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs. Methods: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > $2{\times}UNL$ within the first 8 weeks of anti-TB treatment. Results: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >$2{\times}UNL$ at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). Conclusion: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

Background: A disputed rpoB mutation is a specific type of rpoB mutation that can cause low-level resistances to rifampin (RIF). Here, we aimed to assess the frequency and types of disputed rpoB mutations in Mycobacterium tuberculosis isolates from South Korea. Methods: Between August 2009 and December 2015, 130 patients exhibited RIF resistance on the MTBDRplus assay at Asan Medical Center. Among these cases, we identified the strains with disputed rpoB mutation by rpoB sequencing analysis, as well as among the M. tuberculosis strains from the International Tuberculosis Research Center (ITRC). Results: Among our cases, disputed rpoB mutations led to RIF resistance in at least 6.9% (9/130) of the strains that also exhibited RIF resistance on the MTBDRplus assay. Moreover, at the ITRC, sequencing of the rpoB gene of 170 strains with the rpoB mutation indicated that 23 strains (13.5%) had the disputed mutations. By combining the findings from the 32 strains from our center and the ITRC, we identified the type of disputed rpoB mutation as follows: CTG511CCG (L511P, n=8), GAC516TAC (D516Y, n=8), CTG533CCG (L533P, n=8), CAC526CTC (H526L, n=4), CAC526AAC (H526N, n=3), and ATG515GTG (M515V, n=1). Conclusion: Disputed rpoB mutations do not seem to be rare among the strains exhibiting RIF resistance in South Korea.

Background: Smoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD. Methods: We included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment. Results: The median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036-1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376-29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388-34.998; p=0.018) were related to moderate to high nicotine dependence. Conclusion: Nicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.

Background: We aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible. Methods: This was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield. Results: We included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76-13.72; p=0.002). Conclusion: The presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.

Background: Since the introduction of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. Methods: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. Results: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. Conclusion: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Background: Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). Methods: We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. Results: Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted ${\beta}-coefficient$, -0.19; 95% confidence interval, -1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. Conclusion: Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

Background: Chronic obstructive pulmonary disease (COPD), is a chronic inflammatory disorder. We evaluated whether white blood cell (WBC) count, is associated with the severity of COPD, independent of other inflammatory conditions, such as metabolic syndrome. Methods: The WBC counts were compared between 1227 COPD patients and 8679 non-COPD adults older than 40. The relationships between the WBC count, lung function, and symptoms score in COPD patients, were determined, using general linear regression analyses. Results: The WBC count was negatively associated with forced vital capacity (FVC, L), FVC (% predicted), forced expiry volume in one second ($FEV_1$, L), and $FEV_1$ (% predicted) in COPD patients. Additionally, the WBC count was independently associated with the quality of life measure, by EQ5D-index score. However, this relationship between WBC count, and disease severity, was not significant in current smokers, because of the confounding effect of smoking, on the WBC count. Conclusion: The WBC count is associated with current smoking status and COPD severity, and a risk factor for poor lung function, and quality of life, especially in non-currently smoking COPD patients. The WBC count can be used, as an easily measurable COPD biomarker.