Tae Sun Ha, Dong Kyu Oh, Hak-Jae Lee, Youjin Chang, In Seok Jeong, Yun Su Sim, Suk-Kyung Hong, Sunghoon Park, Gee Young Suh, So Young Park
{"title":"Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.","authors":"Tae Sun Ha, Dong Kyu Oh, Hak-Jae Lee, Youjin Chang, In Seok Jeong, Yun Su Sim, Suk-Kyung Hong, Sunghoon Park, Gee Young Suh, So Young Park","doi":"10.4046/trd.2024.0039","DOIUrl":"10.4046/trd.2024.0039","url":null,"abstract":"<p><strong>Background: </strong>Successful liberation from mechanical ventilation is one of the most crucial processes in critical care, because it is the first step through which a respiratory failure patient begins to transition out of the intensive care unit, and return to normal life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider scientific and systematic approaches, as well as the individual experiences of healthcare professionals. Recently, numerous studies have investigated methods and tools to identify when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians for liberation from the ventilator.</p><p><strong>Methods: </strong>Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. These evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved the recommendations.</p><p><strong>Results: </strong>Recommendations for nine questions on ventilator liberation about Population, Intervention, Comparator, and Outcome (PICO) are presented in this document. This guideline presents seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation.</p><p><strong>Conclusion: </strong>We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"415-439"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sungmin Zo, Ji-Yong Moon, Kyung Hoon Min, Hyun Lee
{"title":"Secondary Immunodeficiency and Non-cystic Fibrosis Bronchiectasis.","authors":"Sungmin Zo, Ji-Yong Moon, Kyung Hoon Min, Hyun Lee","doi":"10.4046/trd.2024.0015","DOIUrl":"10.4046/trd.2024.0015","url":null,"abstract":"<p><p>Bronchiectasis is a chronic respiratory disease characterized by abnormal dilation of the bronchi that causes cough, sputum, and recurrent infections. As it may be associated with various respiratory or systemic diseases, a critical aspect of managing bronchiectasis is to identify the underlying cause. Immunodeficiency is a rare but important cause of bronchiectasis, and its treatability is a significant trait for bronchiectasis management. While primary immunodeficiencies in bronchiectasis are well recognized, secondary immunodeficiencies remain under-reported and under-researched. Secondary immunodeficiencies may result from various diseases and conditions, such as hematologic malignancies, human immunodeficiency virus infection, renal transplantation, or the use of immunosuppressive drugs, and may contribute to the occurrence of bronchiectasis. Recurrent pulmonary and/or extrapulmonary infections in bronchiectasis may indicate the presence of secondary immunodeficiency in patients with these underlying conditions. For treatment, examining the underlying condition, managing bronchiectasis adequately, and prophylactic antibiotics (e.g., macrolide) and/or supplementary immunoglobulin G therapy may provide potential benefits. Considering the projected increase in the prevalence of secondary immunodeficiencies and bronchiectasis, future guidelines and research on the diagnosis and optimized treatment are needed.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"440-450"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Association of Bacterial Coinfections with Clinical Characteristics of Patients with Nontuberculous Mycobacterial Pulmonary Disease.","authors":"Seong Mi Moon, Hyunkyu Cho, Beomsu Shin","doi":"10.4046/trd.2024.0003","DOIUrl":"10.4046/trd.2024.0003","url":null,"abstract":"<p><strong>Background: </strong>Clinical data for bacterial coinfection of the lower respiratory tract in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are scarce. This study aims to assess the prevalence of bacterial coinfection and clinical features in NTM-PD patients.</p><p><strong>Methods: </strong>This retrospective study screened 248 patients with NTM-PD who underwent bronchoscopy between July 2020 and July 2022, from whom newly diagnosed NTM-PD patients were analyzed. Bacterial culture using bronchial washing fluid was performed at the time of NTM-PD diagnosis.</p><p><strong>Results: </strong>In the 180 patients (median age 65 years; 68% female), Mycobacterium avium complex (86%) was the most frequent NTM isolated. Bacterial coinfections were detected in 80 (44%) patients. Among them, the most common bacterium was Klebsiella pneumoniae (n=25/80, 31.3%), followed by Pseudomonas aeruginosa (n=20/80, 25%) and Staphylococcus aureus (n=20/80, 25%). Compared with NTM-PD patients without bacterial coinfections, patients with bacterial coinfections showed more frequent extensive lung involvement (33% vs. 1%, p<0.001). Additionally, compared with NTM-PD patients without P. aeruginosa infection, those with P. aeruginosa infection were older (74 years vs. 64 years, p=0.001), had more frequent respiratory symptoms (cough/excessive mucus production 70% vs. 38%, p=0.008; dyspnea 30% vs. 13%, p=0.047), and had extensive lung involvement (60% vs. 9%, p<0.001).</p><p><strong>Conclusion: </strong>Less than half of patients with newly diagnosed NTM-PD had bacterial coinfections, linked to extensive lung involvement. Specifically, P. aeruginosa coinfection was significantly associated with older age, more frequent respiratory symptoms, and extensive lung involvement.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":"87 4","pages":"505-513"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heesang Han, Ji-Hee Lee, Sung Jun Chung, Beong Ki Kim, Yedham Kang, Hangseok Choi, Hee-Jin Kim, Seung Heon Lee
{"title":"Prevalence and Characteristics of Tuberculosis in the Korean Homeless Population Based on Nationwide Tuberculosis Screening.","authors":"Heesang Han, Ji-Hee Lee, Sung Jun Chung, Beong Ki Kim, Yedham Kang, Hangseok Choi, Hee-Jin Kim, Seung Heon Lee","doi":"10.4046/trd.2023.0197","DOIUrl":"10.4046/trd.2023.0197","url":null,"abstract":"<p><strong>Background: </strong>The government of Korea implemented a strategy of prevention and early diagnosis in high-risk groups to reduce the tuberculosis (TB) burden. This study aims to investigate the TB epidemiology and gap in understanding of TB prevalence among homeless individuals by analyzing active TB chest X-ray (CXR) screening results in Korea.</p><p><strong>Methods: </strong>The Korean National Tuberculosis Association conducted active TB screening with CXR for homeless groups from January 1 to December 31, 2021. Sputum acid-fast bacilli smear and culture were performed for the subjects suggestive of TB on CXR. We performed a cross-sectional analysis of the data in comparison with the national health screening results from the general population.</p><p><strong>Results: </strong>Among 17,713 homeless persons, 40 (0.23%), 3,077 (17.37%), and 79 (0.45%) were categorized as suggested TB, inactive TB, and observation required, respectively. Prevalence of suggested TB in the homeless was significantly higher (3-5 fold) than in Univerthe national general health screening based on age category (p<0.005). Twenty-nine cases were confirmed as TB, yielding a prevalence of 164 cases per 100,000 individuals; 19 of these 29 cases showed inactive TB on CXR. Body mass index (p=0.0478) and CXR result (p<0.001) significantly correlated with confirmed TB based on multivariable analysis.</p><p><strong>Conclusion: </strong>Nutrition status and CXR results, especially that of inactive TB, should be considered in active TB screening of the homeless population, where TB prevalence is higher than the general population.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"514-523"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Da Hyun Kang, Chang-Min Choi, Cheol-Kyu Park, In-Jae Oh, Young-Chul Kim, Seong Hoon Yoon, Yoonjoo Kim, Jeong Eun Lee
{"title":"Immune Checkpoint Inhibitor Score Predicts Survival Benefit of Immunotherapy in Patients with Non-small Cell Lung Cancer.","authors":"Da Hyun Kang, Chang-Min Choi, Cheol-Kyu Park, In-Jae Oh, Young-Chul Kim, Seong Hoon Yoon, Yoonjoo Kim, Jeong Eun Lee","doi":"10.4046/trd.2023.0190","DOIUrl":"10.4046/trd.2023.0190","url":null,"abstract":"<p><strong>Background: </strong>The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs.</p><p><strong>Methods: </strong>This was a prospective multicenter study in patients with advanced nonsmall cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score.</p><p><strong>Results: </strong>A total of 143 patients from four institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p=0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p<0.001).</p><p><strong>Conclusion: </strong>Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"483-493"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang
{"title":"UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer.","authors":"Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang","doi":"10.4046/trd.2023.0166","DOIUrl":"10.4046/trd.2023.0166","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer.</p><p><strong>Methods: </strong>Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated.</p><p><strong>Results: </strong>We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC.</p><p><strong>Conclusion: </strong>UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":"87 4","pages":"494-504"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jong Hwan Jeong, Manbong Heo, Sunghoon Park, Su Hwan Lee, Onyu Park, Taehwa Kim, Hye Ju Yeo, Jin Ho Jang, Woo Hyun Cho, Jung-Wan Yoo
{"title":"Association between Age-Adjusted Endothelial Activation and Stress Index and Intensive Care Unit Mortality in Patients with Severe COVID-19.","authors":"Jong Hwan Jeong, Manbong Heo, Sunghoon Park, Su Hwan Lee, Onyu Park, Taehwa Kim, Hye Ju Yeo, Jin Ho Jang, Woo Hyun Cho, Jung-Wan Yoo","doi":"10.4046/trd.2024.0081","DOIUrl":"10.4046/trd.2024.0081","url":null,"abstract":"<p><strong>Background: </strong>Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea.</p><p><strong>Methods: </strong>Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed.</p><p><strong>Results: </strong>The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p<0.001). log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001).</p><p><strong>Conclusion: </strong>Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"524-531"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study.","authors":"Eun Chong Yoon, Hyewon Lee, Hee-Young Yoon","doi":"10.4046/trd.2024.0038","DOIUrl":"10.4046/trd.2024.0038","url":null,"abstract":"<p><strong>Background: </strong>Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroid (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases.</p><p><strong>Methods: </strong>We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability of treatment weighting (IPTW) to ensure a balanced analysis of covariates.</p><p><strong>Results: </strong>Of the 57,553 patients (mean age 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including nine among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI], 1.48 to 15.58). Higher risks were significant for patients ≥65 years (adjusted HR, 6.40; 95% CI, 1.28 to 31.94), females (adjusted HR, 10.91; 95% CI, 2.24 to 53.20), never-smokers (adjusted HR, 6.31; 95% CI, 1.49 to 26.64), systemic steroid users (adjusted HR, 50.19; 95% CI, 8.07 to 312.19), and those with higher comorbidity scores (adjusted HR, 6.64; 95% CI, 1.19 to 37.03).</p><p><strong>Conclusion: </strong>ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":"473-482"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nakwon Kwak, Joong-Yub Kim, Hyung-Jun Kim, Byoung-Soo Kwon, Jae Ho Lee, Jeongha Mok, Yong-Soo Kwon, Young Ae Kang, Youngmok Park, Ji Yeon Lee, Doosoo Jeon, Jung-Kyu Lee, Jeong Seong Yang, Jake Whang, Kyung Jong Kim, Young Ran Kim, Minkyoung Cheon, Jiwon Park, Seokyung Hahn, Jae-Joon Yim
{"title":"High-dose rifampicin for 3 months after culture conversion for drug-susceptible pulmonary tuberculosis.","authors":"Nakwon Kwak, Joong-Yub Kim, Hyung-Jun Kim, Byoung-Soo Kwon, Jae Ho Lee, Jeongha Mok, Yong-Soo Kwon, Young Ae Kang, Youngmok Park, Ji Yeon Lee, Doosoo Jeon, Jung-Kyu Lee, Jeong Seong Yang, Jake Whang, Kyung Jong Kim, Young Ran Kim, Minkyoung Cheon, Jiwon Park, Seokyung Hahn, Jae-Joon Yim","doi":"10.4046/trd.2024.0099","DOIUrl":"https://doi.org/10.4046/trd.2024.0099","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile. Trial registration ClinicalTrials.gov NCT04485156.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyeon Kyu Choi, Gaeul Bang, Ju Hye Shin, Mi Hwa Shin, Ara Woo, Song Yee Kim, Sang Hoon Lee, Eun Young Kim, Hyo Sup Shim, Young Joo Suh, Ha Eun Kim, Jin Gu Lee, Jinwook Choi, Ju Hyeon Lee, Chul Hoon Kim, Moo Suk Park
{"title":"Regenerative capacity of alveolar type 2 cells is proportionally reduced following disease progression in idiopathic pulmonary fibrosis-derived organoid cultures.","authors":"Hyeon Kyu Choi, Gaeul Bang, Ju Hye Shin, Mi Hwa Shin, Ara Woo, Song Yee Kim, Sang Hoon Lee, Eun Young Kim, Hyo Sup Shim, Young Joo Suh, Ha Eun Kim, Jin Gu Lee, Jinwook Choi, Ju Hyeon Lee, Chul Hoon Kim, Moo Suk Park","doi":"10.4046/trd.2024.0094","DOIUrl":"https://doi.org/10.4046/trd.2024.0094","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology.</p><p><strong>Purpose: </strong>This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.</p><p><strong>Method: </strong>Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells.</p><p><strong>Results: </strong>FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells.</p><p><strong>Conclusion: </strong>This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.</p>","PeriodicalId":23368,"journal":{"name":"Tuberculosis and Respiratory Diseases","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}