Tuberculosis and Respiratory Diseases最新文献

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Background: Current research on nontuberculous mycobacteria (NTM) is multidisciplinary, necessitating proper organization to obtain comprehensive insight. Therefore, a bibliometric analysis was performed to identify NTM research characteristics in South Korea.

Methods: The Web of Science was searched for NTM articles authored by Koreans at Korean institutions until March 2023. We collected data on authors, publication year, article type, study design, research area, citations, research institutes, and funding sources.

Results: Of the 28,092 articles on NTM, Koreans authored 868. After excluding 167 unrelated studies, 701 relevant articles were analyzed. The first study was from 1992, with publication rates markedly increasing from 2004 onward. Basic research constituted 41.3% (n=290) of the papers, whereas clinical research represented 44.7% (n=313). Basic research consisted mostly of biochemistry studies (n=73, 10.4%), whereas clinical research primarily involved retrospective studies (n=118, 16.8%). Fifty-four institutions participated in NTM research, with the top five contributing to 71% (n=498) of the publications. The National Research Foundation of Korea was the most significant funding source, supporting 181 studies (32.5% of funded articles). Citation analysis revealed a median citation count of 10 (interquartile range, 3 to 13), with clinical research dominating the top-cited articles and a rise in publications in high-impact journals over time.

Conclusion: The quality and quantity of NTM research in South Korea has improved. However, it is concentrated in a few institutions and is largely funded by a few sources. Future research should use more diverse funding sources, be conducted in more institutions, and prioritize prospective study designs to enhance the understanding and treatment of NTM.

Background: Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells.

Methods: CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis.

Results: Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells.

Conclusion: CG-745 may represent a novel therapeutic strategy for NSCLC treatment.

Chronic obstructive pulmonary disease (COPD) can be caused by various factors, including lung infections, asthma, air pollution, childhood growth disorders, and genetic factors, though smoking is the predominant risk factor. The main pathological mechanisms in COPD involve small airway disease, emphysema, mucus hypersecretion, and vascular disorders. COPD in non-smokers is characterized by a normal 1-second forced expiratory volume decline, equal sex distribution, younger age of onset, fewer comorbidities, milder airflow obstruction, preserved diffusing capacity of the lungs for carbon monoxide, and radiological features such as more air-trapping and less severe emphysema compared to COPD in smokers. Nevertheless, non-smokers with COPD still experience a high prevalence of acute exacerbations, nearly equal to that of smokers with COPD. Moreover, COPD itself is an independent risk factor for developing lung cancer, regardless of smoking status. Given that COPD coexists with numerous comorbidities, effectively managing these comorbidities is crucial, requiring multifaceted efforts for comprehensive treatment.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen.

Methods: 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. The study is registered with ClinicalTrials.gov (NCT04485156).

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.

Conclusion: The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases characterized by muscle involvement and various extramuscular manifestations. Interstitial lung disease (ILD) is one of the most common extramuscular manifestations of IIM and is associated with significant mortality and morbidity. The clinical phenotypes, treatment responses, and prognosis of IIM-ILD are significantly related to myositis-specific antibody (MSA) profiles, with some racial differences. The features associated with MSA in IIM-ILD could also be relevant to cases of ILD where MSA is present but does not meet the criteria for IIM. The anti-melanoma differentiation-associated gene 5 antibody is highly associated with rapidly progressive ILD (RP-ILD), especially in Asian populations, and with characteristic cutaneous manifestations, such as skin ulcers. Radiologically, ground-glass opacities, consolidations, and nonsegmental linear opacities were more predominant than reticular opacities and honeycombing. While the mortality rate is still around 30%, the prognosis can be improved with early intensive therapy with corticosteroids and multiple immunosuppressants. In contrast, anti-aminoacyl-tRNA synthetase (ARS) antibodies are associated with chronic ILD, although RP-ILD is also common. Patients with anti-ARS antibodies often show lung-predominant presentations, with subtle muscle and skin involvement. Radiologically, reticular opacities, with or without consolidation, are predominant and may progress to honeycombing over time. Combination therapy with corticosteroids and a single immunosuppressant is recommended to prevent relapses, which often lead to a decline in lung function and fatal long-term outcomes. Significant advances in immunology and genetics holds promise for fostering more personalized approaches to managing IIMILD.

Spirometry can play a critical role as a gold standard in the diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD). While the criteria for diagnosis have advanced over time, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) standard of the forced expiratory volume in 1 second/forced vital capacity ratio <0.7 remains the most universally employed metric. However, spirometry cannot be utilized in all situations, and test execution can be difficult for some patients, often showing normal values in the early diagnosis of COPD. Therefore, research on new diagnostic methods is underway. Techniques include whole-body plethysmography for measurement of residual volume and inspiratory capacity and airway resistance, diffusing capacity of carbon monoxide or nitric oxide, impulse oscillometry, infrared time-offlight depth image sensor, diaphragm ultrasonography, which can enable early diagnosis and multifaceted assessment of patients with COPD.