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Kwak Nakwon,Lee Kyoung-Hee,Woo Jisu,Kim Jiyeon,Lee Chang-Hoon,Yoo Chul-Gyu 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
Inflammation, oxidative stress, and protease–antiprotease imbalance have been suggested to be a pathogenic triad in chronic obstructive pulmonary disease (COPD). However, it is not clear how proteases interact with components of inflammatory pathways. Therefore, this study aimed to evaluate the effect of neutrophil elastase (NE) on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production and determine the molecular mechanism in human bronchial epithelial cells (HBECs). Immortalized bronchial epithelial cells and primary HBECs were used to investigate the impact of NE on LPS-induced IL-8 production. The molecular mechanism by which NE modulated LPS-induced IL-8 production was confirmed in elastase-treated C57BL/6 mice and primary HBECs obtained from COPD patients and healthy controls. The results showed that NE treatment synergistically augmented LPS-induced IL-8 production in both immortalized bronchial epithelial cells and primary HBECs. NE partially degraded peroxisome proliferator-activated receptor gamma (PPARγ), which is known to regulate IL-8 production in the nucleus. Treatment with a PPARγ agonist and overexpression of PPARγ reversed the NE-induced synergistic increase in LPS-induced IL-8 production. Moreover, PPARγ levels were lower in lung homogenates and lung epithelial cells from elastase-treated mice than in those from saline-treated mice. In accordance with the findings in mice, PPARγ levels were lower in primary HBECs from COPD patients than in those from healthy never-smokers or healthy smokers. In conclusion, a vicious cycle of mutual augmentation of protease activity and inflammation resulting from PPARγ degradation plays a role in the pathogenesis of COPD.
Host-Directed Therapy for Tuberculosis
( Nakwon Kwak ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0
Tuberculosis (TB) remains the most severe infectious disease. Although the standard treatment regimen for TB (comprising isoniazid, rifampicin, ethambutol, and pyrazinamide) has been proven to be effective, two major concerns remain to be addressed. First, the standard treatment regimen typically requires a minimum 6 months for completion, with this lengthy treatment leading to increased toxicity and poor adherence. Second, many patients develop permanent respiratory impairment even after successful TB eradication. In light of these problems, host-directed therapy (HDT) has gained attention. HDTs, which are adjunctive treatments, exert their effects by enhancing antibacterial mechanisms and reducing inflammation. By improving autophagy and T-cell responses, HDTs accelerate bacillary clearance. Meanwhile, by modulating proinflammatory mediators and dampening inflammation, inflammation-induced tissue injury is prevented and lung function is spared. Based on these properties, HDTs have the potential to shorten treatment duration and reduce lung injury. In this session, the current concept and progression of HDTs will be presented. After reviewing immune responses to Mycobacterium tuberculosis, laboratory data of HDT candidates will be covered. Moreover, clinical data will be presented. Finally, the future role of HDT in the treatment of TB will be proposed.
( Nakwon Kwak ),( Hongjo Choi ),( Doosoo Jeon ),( Byung Woo Jhun ),( Kyung-wook Jo ),( Young Ae Kang ),( Yong-soo Kwon ),( Myungsun Lee ),( Jeongha Mok ),( Tae-sun Shim ),( Hong-joon Shin ),( Jake Wha 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.2
Background: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). Methods: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii ; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants’ clinical course will be tracked and their clinical data as well as NTM isolates will be collected. Conclusion: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.
Mycobacterium abscessus pulmonary disease : individual patient data meta-analysis
( Nakwon Kwak ),( Margareth Pretti Dalcolmo ),( Charles L. Daley ),( Geoffrey Eather ),( Regina Gayoso ),( Naoki Hasegawa ),( Byung Woo Jhun ),( Won-jung Koh ),( Ho Namkoong ),( Jimyung Park ),( Rache 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-
Background: Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), which is caused by subspecies M. abscessus subspecies abscessus (M. abscessus), M. abscessus subspecies massiliense (M. massiliense), or M. abscessus subspecies bolletii, is challenging. Methods: We conducted an individual patient data meta-analysis based on published studies reporting treatment outcomes for MAB-PD to clarify the treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Results: A total of 303 patients with MAB-PD from eight studies were included. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus and 56.7% for M. massiliense pulmonary disease. For MAB-PD, the use of imipenem was associated with treatment success (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.36-5.10). For patients with M. abscessus, the use of azithromycin (aOR, 3.29; 95% CI, 1.26-8.62), amikacin (aOR, 1.44; 95% CI, 1.05-1.99), or imipenem (aOR, 7.96; 95% CI, 1.52-41.6) increased the likelihood of treatment success. For patients with M. massiliense, the choice among these drugs did not affect the treatment outcomes. Conclusion: Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin, or imipenem improves treatment outcomes for patients with M. abscessus pulmonary disease.
Kwak Nakwon,Hwang Ha Won,Kim Hyung-Jun,Lee Hyun Woo,Yim Jae-Joon,Lee Chang-Hoon 대한의학회 2022 Journal of Korean medical science Vol.37 No.26
This study aimed to investigate the association between Bacille Calmette-Guérin (BCG) vaccination and nontuberculous mycobacterial pulmonary disease (NTM-PD). Patients in the prospective NTM-PD cohort were matched to healthy controls to measure the association between BCG and NTM-PD development. The clinical course of NTM-PD patients was also evaluated to investigate the association between BCG and NTM-PD progression. BCG scars were not associated with NTM-PD development (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 0.96–4.34) or progression (adjusted OR, 1.61; 95% CI, 0.92–2.81). In conclusion, BCG vaccination was not associated with the development or progression of NTM-PD.
( Jinyoung Moon ),( Nakwon Kwak ),( Jin Lim ),( Dong Jin Go ),( Jae Hyun Lee ),( Jin Kyun Park ),( Eun Bong Lee ),( Yeong Wook Song ),( Jai Il Youn ),( Eun Young Lee ) 대한류마티스학회 2015 대한류마티스학회지 Vol.22 No.4
Nowadays, tumor necrosis factor-α (TNF-α) blockers are used for treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Paradoxically, there are some reports on the appearance of psoriasis after administration of TNF-α blockers. Here, we report on a patient with monoarthritis in a knee joint who experienced psoriasis after TNF-α blocker therapy (adalimumab and etanercept). Oral medication was not a treatment option due to patient intolerance; thus, we tried ustekinumab, an anti-interleukin (IL)-12/23 monoclonal antibody used for treatment of psoriasis. Following ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved. However, in the following period, joint pain and swelling became aggravated and synovial fluid cytokine levels including IL-6 and IL-17 were elevated. The treatment was changed to tocilizumab, a humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesions. (J Rheum Dis 2015;22:263-268)
( Yeon Wook Kim ),( Nakwon Kwak ),( Moon Woo Seong ),( Eui Chong Kim ),( Chul Gyu You ),( Young Whan Kim ),( Sung Koo Han ),( Jae Joon Yim ) 대한결핵 및 호흡기학회 2014 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.118 No.-
Background: The Xpert MTB/RIF assay is endorsed by the WHO for detecting pulmonary and extrapulmonary tuberculosis (EPTB). The aim of this study was to determine the accuracy of the Xpert MTB/RIF assay in diagnosing EPTB in South Korea, which has an intermediate TB burden. Methods: We retrospectively reviewed the medical records of 1,426 patients in whom the Xpert MTB/RIF assay using extrapulmonary specimens was requested between January 1, 2011 and October 31, 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosis of EPTB and detection of rifampicin resistance were calculated. Results: Using culture as gold standard, sensitivity, specificity, PPV, and NPV of the assay were 67.7%, 98.1%, 60%, and 98.6%, respectively. Higher sensitivity was shown among specimens including needle aspirates and biopsied tissues (85.7%), pus (75%), joint fluids (100%), and urine (100%). The sensitivity, specificity, PPV, and NPV for the detection of rifampicin resistance among specimens with positive results for M. TB were 80%, 100%, 100%, and 97.7%, respectively. Conclusions: The Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for diagnosis of EPTB and detection of rifampicin resistance in a country with an intermediate TB burden.
( So Jeong Kim ),( Nakwon Kwak ),( Sun Mi Choi ),( Jinwoo Lee ),( Young Sik Park ),( Chang-hoon Lee ),( Sang-min Lee ),( Chul-gyu Yoo ),( Young Whan Kim ),( Jaeyoung Cho ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Background: In general populations, extreme sleep duration negatively affects health-related quality of life (HRQOL). However, association of sleep duration with HRQOL in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. Methods: We analyzed 2,157 participants with COPD enrolled in the 2007-2015 Korea National Health and Nutrition Examination Survey (KNHANES). Participants were eligible for current study if they were 40 years or older with smoking history and had pre-bronchodilator forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) < 0.7. Participants were categorized into three groups according to self-reported sleep duration < 6 (short sleeper), 6-8, and > 8 hours (long sleeper). HRQOL was measured with the European Quality of Life-5 Dimensions (EQ-5D) index and visual analogue scale (VAS). Since EQ VAS from 2013 to 2015 KNHANES was not included in the survey, data from 1,436 patients with COPD were analyzed for EQ VAS. Results: In multiple linear regression adjusting for sociodemographics, body mass index, FEV1, and comorbidities, long sleep duration was associated with lower EQ-5D index (β=-0.024; 95% confidence interval [CI], -0.043 to -0.005) and lower EQ VAS (β=- 5.5; 95% CI, -8.8 to -2.1). The adjusted EQ-5D index was 0.911 (95% CI, 0.899 to 0.923) for short sleepers, 0.929 (95% CI, 0.922 to 0.934) for 6 to 8-hour sleepers, 0.900 (95% CI, 0.882 to 0.917) for long sleepers (P=0.002). The adjusted EQ VAS was 71.4 (95% CI, 69.2 to 73.5) for short sleepers, 73.6 (95% CI, 72.5 to 74.7) for 6 to 8-hour sleepers, 67.5 (95% CI, 64.4 to 70.7) for long sleepers (P=0.001). In sensitivity analysis of 1,134 patients with COPD whose FEV1 < 80% predicted, long sleep duration was associated with lower EQ-5D index (β=-0.031) and lower EQ VAS (β=-4.7). Conclusions: In patients with COPD, long sleep duration was independently associated with worse HRQOL.