Search

Latent tuberculosis infection (LTBI) is characterized by immune responses to Mycobacterium tuberculosis antigens without clinical symptoms or evidence of active tuberculosis. Effective LTBI management is crucial for tuberculosis elimination, requiring accurate diagnosis and treatment. In South Korea, LTBI guidelines have been updated periodically, with the latest in 2024. This review discusses the recent changes in the Korean guideline for the diagnosis and treatment of LTBI in adults.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen., Method: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates., Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups., Conclusions: The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile. Trial registration ClinicalTrials.gov NCT04485156.

Background: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), clinical characteristics show geographical variations. We investigated the clinical characteristics of patients with NTM-PD in South Korea., Methods: We systematically reviewed articles concerning patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form., Results: Data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5±11.7 years, of whom 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and M. abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Although reported cases of NTM-PD increased over the years, the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 years vs. 59.9 years, p&lt;0.001), and had more cavitary lesions than women (38.8% vs. 21.0%, p&lt;0.001). The older group (≥65 years) had higher proportions of patients with body mass index &lt;18.5 kg/m2 (27.4% vs. 18.6%, p&lt;0.001) and cavitary lesions (29.9% vs. 27.6%, p=0.009) than the younger group., Conclusion: We conducted a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea, and found age- and sex-related differences in disease- specific severity. Further investigation would enhance our comprehension of the nature of the disease, and inherited and acquired host factors.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea., Methods: A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis., Results: More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis., Conclusion: Based on this Delphi survey, experts' agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting., Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included., Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success)., Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

Background: Flexible bronchoscopy is one of the essential procedures for the diagnosis and treatment of pulmonary diseases. The purpose of this study was to identify the risk factors associated with the occurrence of hypoxia in adults undergoing flexible bronchoscopy under sedation., Methods: We retrospectively analyzed 2,520 patients who underwent flexible bronchoscopy under sedation at our tertiary care university hospital in South Korea January 1, 2013-December 31, 2014. Hypoxia was defined as more than 5%-point reduction in the baseline percutaneous oxygen saturation (SpO2) or SpO2 <90% for >1 minute during the procedure., Results: The mean age was 64.7±13.5, and 565 patients developed hypoxia during the procedure. The mean sedation duration and midazolam dose for sedation were 31.1 minutes and 3.9 mg, respectively. The bivariate analysis showed that older age, a low forced expiratory volume in one second (FEV1), use of endobronchial ultrasound, the duration of sedation, and the midazolam dose were associated with the occurrence of hypoxia during the procedure, while the multivariate analysis found that age >60 (odds ratio [OR], 1.32), a low FEV1 (OR, 0.99), and a longer duration of sedation (>40 minutes; OR, 1.33) were significant risk factors., Conclusion: The findings suggest that patients older than age 60 and those with a low FEV1 tend to develop hypoxia during the bronchoscopy under sedation. Also, longer duration of sedation (>40 minutes) was a significant risk factor for hypoxia.

Background: North Korea is one of the 30 countries with the highest tuberculosis (TB) and drug-resistant TB burdened. To understand the medical issues and research trends associated with TB in North Korea, we performed a comprehensive review of articles related to clinical and laboratory research on TB published in North Korean medical journals., Methods: We reviewed all types of TB-related articles published in nine North Korean medical journals (Yebang ŭihak: Preventive medicine; Koryo ŭihak: Korea Medicine; Chosŏn ŭihak: Chosun Medicine; Naekwa: Internal Medicine; Soa, sanbuinkwa: Pediatrics, Obstetrics, and Gynecology, Surgery; Ŭihak: Medicine; Kich'o ŭihak: Basic Medicine; and Chosŏn yakhak: Chosun Pharmacy). We classified the articles according to the type and field of study and analyzed the data qualitatively to gain insights., Results: We reviewed 106 articles (one- or two-page length) written in Korean, including reviews (n=43), original articles (n=52), and case reports (n=8). They were classified as follows: articles on diagnosis (n=52, 49%) and treatment (n=39, 37%). None of the studies investigated the commercialized molecular diagnosis systems such as Xpert MTB/RIF. Directly Observed Treatment, Short-course was reported as the basic treatment approach. Furthermore, six studies used Korean traditional medicines for treating TB, with one of them containing snake venom., Conclusion: The articles were not sufficiently detailed. Original articles on the treatment of multi-drug resistant TB were not found, and those on latent tuberculosis infection and nontuberculous mycobacteria were limited. To understand the current medical issues associated with TB in North Korea, articles from these nine journals were not sufficient.

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., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2020. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Background: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1., Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks., Results: When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks., Conclusion: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro , and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo . Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Pneumonia is an important cause of morbidity and mortality. Since 2014, the Health Insurance Review and Assessment Service (HIRA) has assessed the overall quality of care among hospitalized adult patients with community-acquired pneumonia (CAP) provided by all medical institutions in Korea. A committee of the Korea Academy of Tuberculosis and Respiratory Diseases developed the hospital inpatient quality measures set for CAP consisting of eight core measures and five monitoring measures. The composite measure score was calculated. The medical records of hospitalized adult patients ages 18 years or more with CAP from October to December 2014 were evaluated. The data of 523 hospitals (42 tertiary hospitals [8.0%], 256 general hospitals [49%], and 225 hospitals [43.0%]) and 15,432 cases (tertiary hospitals, 1,673 cases [10.8%]; general hospitals, 8,803 cases [57.1%]; hospitals, 4,956 cases [32.1%]) were analyzed. We found large variations among institutions in terms of performance of care measures for CAP. For the composite measure score, the mean value was 66.7 (tertiary hospitals, 98.5; general hospitals, 79.2; hospitals, 43.8). Despite significant differences in measure scores between tertiary, general hospitals and hospitals, no significant differences were found in mortality between hospitals. Further studies are needed to determine the care measures appropriate for CAP., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury., Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure)., Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs. 11.45±1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines., Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

Tuberculosis is a significant infectious problem in elderly patients with comorbidities in Korea. The age-associated diseases such as malignancy and diabetes mellitus may increase the risk of tuberculosis in this population. The medication treatments of tuberculosis in patients with comorbidities can cause adverse reactions to antituberculosis drugs and inadequate treatment responses. Thus, clinicians must carefully monitor the toxicity of antituberculosis therapy and the efficacy of treatment in patients with comorbidities.

Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP.

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-β1 initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain., Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009., Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018)., Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.

A 52-year-old man was referred to our clinic for an 11.3 mm nodule in the left lower lobe that was discovered on a chest computed tomography (CT) scan. Eleven small nodules were subsequently found in both lungs. Initially, we performed a transthoracic needle aspiration using CT scan guidance. The pathologic report showed a few clusters of atypical cells that were suspicious for malignancy. The positron emission tomography images revealed multiple lung nodules scattered throughout both lungs. The largest nodule (11.3 mm) in the left lower lobe did not have any discernible fludeoxyglucose uptake. For pathologic confirmation, we consulted a thoracic surgeon to perform the video-assisted thoracoscopic surgery. The final diagnosis was minute pulmonary meningothelial-like nodules (MPMNs). MPMNs are benign in nature, and only a few cases require treatment. However, when clinicians are suspicious of potential malignancy, a pathological correlation is essential, even if the final diagnosis is MPMNs.

A 43-year-old woman with breast cancer who was on neoadjuvant chemotherapy presented with cough, sputum and mild fever. High-resolution computed tomography showed diffuse ground glass opacities in bilateral lungs and subpleural patchy consolidations. Initially, she was thought to have pneumonia or interstitial lung diseases such as drug-induced pneumonitis and treated with antibiotics and steroids. She subsequently got breast cancer surgery because of disease progression, and concurrent thoracoscopic lung biopsy revealed metastatic carcinoma of the lung from breast cancer. The diagnosis of suspected interstitial lung disease can be made without lung biopsy, but malignancy should always be considered and lung biopsy should be performed in the absence of a definitive clinical diagnosis.

A 55-year-old woman was admitted for an elevated serum carbohydrate antigen-125 (CA-125) level, and a left pleural effusion, which were detected at a routine health examination. Computed tomography of the chest was performed upon admission, revealing extensive bilateral paratracheal and mediastinal lymph node enlargement with a massive left-sided pleural effusion. Subsequent analysis of the pleural fluid demonstrated consistency with an exudate, no evidence of malignant cells, and a normal adenosine deaminase. However, the pleural fluid and serum CA-125 levels were 2,846.8 U/mL and 229.5 U/mL, respectively. A positron emission tomography did not reveal any primary focus of malignancy. Finally, a surgical mediastinoscopic biopsy of several mediastinal lymph nodes was performed, revealing non-necrotizing granulomas, consistent with sarcoidosis. After a month of treatment of prednisolone, the left pleural effusion had resolved, and after 2 months the serum CA-125 level was normalized.

Background: The level of urine cotinine is an indicator of tobacco smoke exposure. The purpose of this study is to investigate urine cotinine for the purpose of assessing the smoking status of Korean smokers and non-smokers exposed to tobacco smoke., Methods: The subjects were identified from the 2007-2009 and the 2010 data sets of the Korea National Health and Nutrition Examination Survey (KNHANES). They were assigned as non-smokers, current smokers and ex-smokers. Non-smokers were also divided into three subset groups according to the duration of smoke exposure. Each group was stratified by gender prior to analysis., Results: The median value of urine cotinine in the male current smokers was 1,221.93 ng/mL which was the highest among all groups. The difference between levels of urine cotinine for male and the female groups was statistically significant (p<0.01). In the female group, passive smoke exposure groups reported higher urine cotinine levels than non-exposure groups (p=0.01). The cutoff point for the discrimination of current smokers from non-smokers was 95.6 ng/mL in males and 96.8 ng/mL in females. The sensitivity and specificity were 95.2% and 97.1%, respectively, in males, 96.1% and 96.5% in females. However, the determination of urine cotinine level was not useful in distinguishing between passive smoke exposure groups and non-exposure groups., Conclusion: Urine cotinine concentration is a useful biomarker for discriminating non-smokers from current smokers. However, careful interpretation is necessary for assessing passive smoke exposure by urine cotinine concentration.