Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model < 대한결핵 및 호흡기학회 < KISS

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대한결핵 및 호흡기학회> Tuberculosis and Respiratory Diseases> Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

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Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

Tai Joon An , Chin Kook Rhee , Ji Hye Kim , Young Rong Lee , Jin Young Chon , Chan Kwon Park , Hyoung Kyu Yoon
  • : 대한결핵 및 호흡기학회
  • : Tuberculosis and Respiratory Diseases 81권1호
  • : 연속간행물
  • : 2018년 01월
  • : 80-87(8pages)

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Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids.
Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed.
Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon g, and tumor necrosis factor a in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05).
Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

UCI(KEPA)

I410-ECN-0102-2018-500-004216731

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  • : 의약학분야  > 내과학
  • : KCI 등재
  • : - / SCOPUS
  • : 계간
  • : 1738-3536
  • :
  • : 학술지
  • : 연속간행물
  • : 1954-2019
  • : 4908


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1Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid

저자 : Michael Dreher , Tobias Muller

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 1-5 (5 pages)

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Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as “severe” asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

2Treatment of Latent Tuberculosis Infection and Its Clinical Efficacy

저자 : Hyung Woo Kim , Ju Sang Kim

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 6-12 (7 pages)

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The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB―those with frequent exposure to active TB cases, and those with clinical risk factors (e.g., immunocompromised patients). Recently revised National Institute for Health and Care Excellence (NICE) guideline recommended that close contacts of individuals with active pulmonary or laryngeal TB, aged between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI treatment were recommended in NICE, World Health Organization (WHO), and Centers for Disease Control and Prevention guidelines, and superiority of one recommended regimen over another was not yet established. Traditional 6 to 9 months of isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for clinical efficacy―60%-90% of estimated protective effect. However, 6H or 9H regimen is related with hepatotoxicity and low compliance. Four months of rifampin regimen is characterized by less hepatotoxicity and better compliance than 9H, but has few evidence of clinical efficacy. Three months of isoniazid plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy and safety, which was recommended in NICE and WHO guidelines. The clinical efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was demonstrated recently, which is not yet introduced into South Korea.

3The Role of Tiotropium+Olodaterol Dual Bronchodilator Therapy in the Management of Chronic Obstructive Pulmonary Disease

저자 : David M. G. Halpin , D. Phil. M. B. B. S. , F. R. C. P.

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 13-18 (6 pages)

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Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β2 agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy. The TOviTO programme has investigated the benefits of treatment with a combination of tiotropium and olodaterol administered via a single inhaler. Tiotropium+olodaterol 5/5 μg significantly improved forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours, trough FEV1 health status and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol 5/5 μg also increased endurance time and reduced dynamic hyperinflation during constant work rate cycle ergometry. On the basis of these and other studies the 2017 GOLD report recommends escalating to dual bronchodilator therapy in patients in groups B and C if they remain symptomatic or continue to have exacerbations and as initial therapy for patients in group D.

4Indicators and Qualitative Assessment of Lung Cancer Management by Health Insurance Review and Assessment Service (HIRA) of Korea in 2015

저자 : Chang Dong Yeo , Myoung Kyu Lee , Seung Hyeun Lee , Eun Young Kim , Ik Jae Lee , Heae Surng Park , Yoon Soo Chang

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 19-28 (10 pages)

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Cancer is the leading cause of death in the Republic of Korea and cancer death accounts for 27.8% of the total deaths, which is not only a social issue but also a concern for the public. Among the cancer death rates, lung cancer mortality account for 34 deaths per 100,000 populations, making it the number one cancer death rate. In a preliminary report on cancer death in 2012, the lung cancer mortality ratio showed the regional variation indicating that there were differences in the qualitative level and the structure among the medical care benefit agency and in the assessment of the treatment process. Therefore, the Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the assessment of lung cancer treatment since 2014 to improve the quality of lung cancer care through evaluation and feeds back the results of lung cancer care process. In this report, authors described the current Indicators for the lung cancer adequacy assessment proposed by HIRA and results of the evaluation reported in 2017.

5Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

저자 : Chi Young Jung , Scott J. Antonia

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 29-41 (13 pages)

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Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immuno-oncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.

6Development of Prediction Equation of Diffusing Capacity of Lung for Koreans

저자 : Yong Il Hwang , Yong Bum Park , Hyoung Kyu Yoon , Seong Yong Lim , Tae-hyung Kim , Joo Hun Park , Won-yeon Lee , Seong Ju Park , Sei Won Lee , Woo Jin Kim , Ki Uk Kim , Kyeong Cheol Shin , Do Jin Kim ,

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 42-48 (7 pages)

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Background: The diffusing capacity of the lung is influenced by multiple factors such as age, sex, height, weight, ethnicity and smoking status. Although a prediction equation for the diffusing capacity of Korea was proposed in the mid-1980s, this equation is not used currently. The aim of this study was to develop a new prediction equation for the diffusing capacity for Koreans.
Methods: Using the data of the Korean National Health and Nutrition Examination Survey, a total of 140 nonsmokers with normal chest X-rays were enrolled in this study.
Results: Using linear regression analysis, a new predicting equation for diffusing capacity was developed. For men, the following new equations were developed: carbon monoxide diffusing capacity (DLco)=-10.4433-0.1434×age (year)+0.2482×heights (cm); DLco/alveolar volume (VA)=6.01507-0.02374×age (year)-0.00233×heights (cm). For women the prediction equations were described as followed: DLco=-12.8895-0.0532×age (year)+0.2145×heights (cm) and DLco/VA=7.69516-0.02219×age (year)-0.01377×heights (cm). All equations were internally validated by k-fold cross validation method.
Conclusion: In this study, we developed new prediction equations for the diffusing capacity of the lungs of Koreans. A further study is needed to validate the new predicting equation for diffusing capacity.

7Detection of Deep Vein Thrombosis by Follow-up Indirect Computed Tomography Venography after Pulmonary Embolism

저자 : Hye Jin Lee , Seung-ick Cha , Kyung-min Shin , Jae-kwang Lim , Seung-soo Yoo , Shin-yup Lee , Jaehee Lee , Chang-ho Kim , Jae-yong Park

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 49-58 (10 pages)

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Background: Information regarding the incidence and risk factors for deep vein thrombosis (DVT) detected by follow-up computed tomographic (CT) venography after pulmonary embolism (PE) is sparse. The aim of the present study was to identify the predictors of DVT in follow-up CT images, and to elucidate their clinical significance.
Methods: Patients with PE were classified into the following three cohorts based on the time of indirect CT venography follow-up: within 1 month, 1 to 3 months, and 3 to 9 months after the initial CT scan. Each cohort was subdivided into patients with or without DVT detected by follow-up CT. Clinical variables were compared between the two groups.
Results: Follow-up CT revealed DVT in 61% of patients with PE within 1 month, in 15% of patients with PE at 1 to 3 months, and in 9% of patients with PE at 3 to 9 months after the initial CT scan. Right ventricular (RV) dilation on the initial CT (odds ratio [OR], 8.30; 95% confidence interval [CI], 1.89-36.40; p=0.005) and proximal DVT at the initial presentation (OR, 6.93; 95% CI, 1.90-25.20; p=0.003) were found to independently predict DVT in follow-up CT images within 1 month, proximal DVT at the initial presentation was found to independently predict DVT in follow-up CT images at 1 to 3 months (OR, 6.69; 95% CI, 1.53-29.23; p=0.012), and central PE was found to independently predict DVT in follow-up CT images at 3 to 9 months (OR, 4.25; 95% CI, 1.22-4.83; p=0.023) after the initial CT scan. Furthermore, the detection of DVT by follow-up CT independently predicted the recurrence of venous thromboembolism (VTE) (OR, 4.67; 95% CI, 2.24-9.74; p<0.001).
Conclusion: Three months after PE, DVT was not detected by follow-up CT in most patients with PE. RV dilation on the initial CT, central PE, and proximal DVT at the initial presentation were found to predict DVT on follow-up CT, which might predict VTE recurrence.

8Comparison of Interferon-γ Release Assays and the Tuberculin Skin Test for Diagnosis of Tuberculosis in Human Immunodeficiency Virus: A Systematic Review

저자 : Kristen Overton , B. Sc. , M. B. B. S. , M. P. H. T. M. , Rick Varma , Mb. Ch. B. , M. R. C. P. u. K. , F. A. Ch. S. H. M. , Dip. Hiv , Dip. Gum , D. T. M. &h. ) , D. F. F. P. , Jeffrey J. Post , M. B. B.

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 59-72 (14 pages)

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Background: It remains uncertain if interferon-γ release assays (IGRAs) are superior to the tuberculin skin test (TST) for the diagnosis of active tuberculosis (TB) or latent tuberculosis infection (LTBI) in immunosuppressed populations including people with human immunodeficiency virus (HIV) infection. The purpose of this study was to systematically review the performance of IGRAs and the TST in people with HIV with active TB or LTBI in low and high prevalence TB countries.
Methods: We searched the MEDLINE database from 1966 through to January 2017 for studies that compared results of the TST with either the commercial QuantiFERON-TB Gold in Tube (QFTGT) assay or previous assay versions, the T-SPOT.TB assay or in-house IGRAs. Data were summarized by TB prevalence. Tests for concordance and differences in proportions were undertaken as appropriate. The variation in study methodology was appraised.
Results: Thirty-two studies including 4,856 HIV subjects met the search criteria. Fourteen studies compared the tests in subjects with LTBI in low TB prevalence settings. The QFTGT had a similar rate of reactivity to the TST, although the first-generation version of that assay was reactive more commonly. IGRAs were more frequently positive than the TST in HIV infected subjects with active TB. There was considerable study methodology and population heterogeneity, and generally low concordance between tests. Both the TST and IGRAs were affected by CD4 T-cell immunodeficiency.
Conclusion: Our review of comparative data does not provide robust evidence to support the assertion that the IGRAs are superior to the TST when used in HIV infected subjects to diagnose either active TB or LTBI.

9Osteoporosis in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome

저자 : Jee Youn Oh , Young Seok Lee , Kyung Hoon Min , Sung Yong Lee , Jae Jeong Shim , Kyung Ho Kang , Gyu Young Hur

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 73-79 (7 pages)

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Background: Osteoporosis is a common disease that occurs comorbidly in patients with chronic inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap syndrome (ACOS). However, the prevalence of osteoporosis in patients with ACOS has not widely been evaluated. Therefore, we investigated the prevalence of osteoporosis and its relationship with the clinical parameters of patients with asthma, COPD, and ACOS.
Methods: This was a retrospective, cross-sectional study. Bone mineral density (BMD), lung function tests, and disease status evaluations were conducted.
Results: A total of 321 patients were enrolled: 138 with asthma, 46 with ACOS, and 137 with COPD. One hundred and ninety-three patients (60.1%) were diagnosed with osteoporosis (53.6% of asthma, 65.2% of ACOS, and 65.0% of COPD). Patients with ACOS showed a significantly lower BMD and T-score than did those with asthma. In addition to age, sex, and body mass index (BMI), which were previously reported to be associated with BMD, BMD also had a negative correlation with the diagnosis of ACOS, as compared to a diagnosis of asthma, after adjusting for age, sex, BMI, smoking, and inhaled corticosteroid use (p=0.001). Among those patients with COPD and ACOS, BMD was negatively associated with the COPD Assessment Test (CAT) after adjustment (p<0.001). Inhaled corticosteroid was not associated with the prevalence of osteoporosis and BMD.
Conclusion: Patients with ACOS, particularly aged and lean women, should be more carefully monitored for osteoporosis as compared to patients with asthma.

10Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

저자 : Tai Joon An , Chin Kook Rhee , Ji Hye Kim , Young Rong Lee , Jin Young Chon , Chan Kwon Park , Hyoung Kyu Yoon

발행기관 : 대한결핵 및 호흡기학회 간행물 : Tuberculosis and Respiratory Diseases 81권 1호 발행 연도 : 2018 페이지 : pp. 80-87 (8 pages)

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Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids.
Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed.
Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon g, and tumor necrosis factor a in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05).
Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

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