Tuberculosis and Respiratory Diseases最新文献

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

In cases where pulmonary tuberculosis (PTB) is not microbiologically diagnosed via sputum specimens, bronchoscopy has been the conventional method to enhance diagnostic rates. Although the additional benefit of bronchoscopy in diagnosing PTB is well-known, its overall effectiveness remains suboptimal. This review introduces several strategies for improving PTB diagnosis via bronchoscopy. First, it discusses how bronchoalveolar lavage or an increased number of bronchial washings can increase specimen abundance. Second, it explores how thin or ultrathin bronchoscopes can achieve specimen acquisition closer to tuberculosis (TB) lesions. Third, it highlights the importance of conducting more sensitive TB-polymerase chain reaction tests on bronchoscopic specimens, including the Xpert MTB/RIF assay and the Xpert MTB/RIF Ultra assay. Finally, it surveys the implementation of endobronchial ultrasound with a guide sheath for tuberculomas, collection of post-bronchoscopy sputum, and reduced use of lidocaine for local anesthesia. A strategic combination of these approaches may enhance the diagnostic rates in PTB patients undergoing bronchoscopy.

The continuously increasing prevalence of severe asthma has imposed an increasing burden worldwide. Despite the emergence of novel therapeutic agents, management of severe asthma remains challenging. Insights garnered from big data may be helpful in the effort to determine the complex nature of severe asthma. In the field of asthma research, a vast amount of big data from various sources, including electronic health records, national claims data, and international cohorts, is now available. However, understanding of the strengths and limitations is required for proper utilization of specific datasets. Use of big data, along with advancements in artificial intelligence techniques, could potentially facilitate the practice of precision medicine in management of severe asthma.

Background: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported.

Methods: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour.

Results: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention.

Conclusion: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.