Endotypes of Exacerbation in Bronchiectasis: An Observational Cohort Study.

Rationale: Bronchiectasis is characterized by acute exacerbations, but the biological mechanisms underlying these events are poorly characterized. Objectives: To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. Methods: A total of 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months. Spontaneous sputum samples were obtained during a period of clinical stability and again at exacerbation before receipt of antibiotic treatment. A validated rapid PCR assay for bacteria and viruses was used to classify exacerbations as bacterial, viral, or both. Sputum inflammatory assessments included label-free liquid chromatography-tandem mass spectrometry and measurement of sputum cytokines and neutrophil elastase activity. 16 s rRNA sequencing was used to characterize the microbiome. Measurements and Main Results: Bronchiectasis exacerbations showed profound molecular heterogeneity. At least one bacterium was identified in 103 samples (86%), and a high bacterial load (total bacterial load > 107 copies/g) was observed in 81 patients (68%). Respiratory viruses were identified in 55 (46%) patients, with rhinovirus being the most common virus (31%). PCR testing was more sensitive than culture. No consistent change in the microbiome was observed at exacerbation. Exacerbations were associated with increased neutrophil elastase, proteinase-3, IL-1ß, and CXCL8. These markers were particularly associated with bacterial and bacterial plus viral exacerbations. Distinct inflammatory and microbiome profiles were seen between different exacerbation subtypes, including bacterial, viral, and eosinophilic events in both hypothesis-led and hypothesis-free analysis using integrated microbiome and proteomics, demonstrating four subtypes of exacerbation. Conclusions: Bronchiectasis exacerbations are heterogeneous events with contributions from bacteria, viruses, and inflammatory dysregulation.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials (RCTs) have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent RCTs.

Genetic characterization of a locus responsible for low pungency using EMS-induced mutants in Capsicum annuum L.

KEY MESSAGE: The pepper mutants ('221-2-1a' and '1559-1-2h') with very low pungency were genetically characterized. The Pun4 locus, responsible for the reduced pungency of the mutant fruits, was localized to a 208 Mb region on chromosome 6. DEMF06G16460, encoding 3-ketoacyl-CoA synthase, was proposed as a strong candidate gene based on the genetic analyses of bulked segregants, DEG, and expression analyses. Capsaicinoids are unique alkaloids present in pepper (Capsicum spp.), synthesized through the condensation of by-products from the phenylpropanoid and branched-chain fatty acid pathways, and accumulating in the placenta. In this study, we characterized two allelic ethyl methanesulfonate-induced mutant lines with extremely low pungency ('221-2-1a' and '1559-1-2h'). These mutants, derived from the pungent Korean landrace 'Yuwolcho,' exhibited lower capsaicinoid content than Yuwolcho but still contained a small amount of capsaicinoid with functional capsaicinoid biosynthetic genes. Genetic crosses between the mutants and Yuwolcho or pungent lines indicated that a single recessive mutation was responsible for the low-pungency phenotype of mutant 221-2-1a; we named the causal locus Pungency 4 (Pun4). To identify Pun4, we combined genome-wide polymorphism analysis and transcriptome analysis with bulked-segregant analysis. We narrowed down the location of Pun4 to a 208-Mb region on chromosome 6 containing five candidate genes, of which DEMF06G16460, encoding a 3-ketoacyl-CoA synthase associated with branched-chain fatty acid biosynthesis, is the most likely candidate for Pun4. The expression of capsaicinoid biosynthetic genes in placental tissues in Yuwolcho and the mutant was consistent with the branched-chain fatty acid pathway playing a pivotal role in the lower pungency observed in the mutant. We also obtained a list of differentially expressed genes in placental tissues between the mutant and Yuwolcho, from which we selected candidate genes using gene co-expression analysis. In summary, we characterized the capsaicinoid biosynthesis-related locus Pun4 through integrated of genetic, genomic, and transcriptome analyses. These findings will contribute to our understanding of capsaicinoid biosynthesis in pepper.

Trajectory of lung function in diabetic adults: A 16-year follow-up study of community-based prospective cohorts.

BACKGROUND AND OBJECTIVE: To investigate the difference in lung function according to diabetes status in a community-based prospective study. METHODS: Individuals aged 40-69 years from two community-based cohorts were followed prospectively for 16 years. A spirometer was used to evaluate lung function at baseline, and lung function tests were carried out biennially thereafter. Multivariable linear regression analysis was performed for the cross-sectional and longitudinal analyses based on diabetes status. RESULTS: Among the 6483 subjects, 2114 (32.6%) had prediabetes and 671 (10.4%) had diabetes. The prediabetes and diabetes groups had lower baseline % predicted values of forced expiratory volume in 1 s (FEV1) (mean, -1.853; 95% confidence interval [CI] -2.715 to -0.990 for prediabetes and mean, -4.088; 95% CI -5.424 to -2.752 for diabetes) and forced vital capacity (FVC) (mean, -2.087; 95% CI -2.837 to -1.337 for prediabetes and mean, -4.622; 95% CI -5.784 to -3.460 for diabetes) compared to the normoglycemia group after adjusting for relevant covariates. The rate of decline in FEV1% predicted (mean, -0.227; 95% CI -0.366 to -0.089) and FVC % predicted (mean, -0.232; 95% CI -0.347 to -0.117) during follow-up were faster in the diabetes group than in the normoglycemia group. The diabetes group had a lower proportion of normal ventilation (ptrend = 0.048) and higher proportions of restrictive (ptrend = 0.001) and mixed (ptrend = 0.035) ventilatory disorders at the last follow-up. CONCLUSION: Diabetes is associated with a lower baseline lung function and a faster rate of deterioration.

Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study.

Rationale: Although inflammation and infection are key disease drivers in bronchiectasis, few studies have integrated host inflammatory and microbiome data to guide precision medicine. Objectives: To identify clusters among patients with bronchiectasis on the basis of inflammatory markers and to assess the association between inflammatory endotypes, microbiome characteristics, and exacerbation risk. Methods: Patients with stable bronchiectasis were enrolled at three European centers, and cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Clusters were compared in terms of microbiome composition (16S ribosomal RNA sequencing) and exacerbation risk over a 12-month follow-up. Measurements and Main Results: A total of 199 patients were enrolled (109 [54.8%] female; median age, 69 yr). Four clusters of patients were defined according to their inflammatory profiles: cluster 1, milder neutrophilic inflammation; cluster 2, mixed-neutrophilic and type 2; cluster 3, most severe neutrophilic; and cluster 4, mixed-epithelial and type 2. Lower microbiome diversity was associated with more severe inflammatory clusters (P < 0.001), and ß-diversity analysis demonstrated distinct microbiome profiles associated with each inflammatory cluster (P = 0.001). Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more enriched in clusters 2 and 3 than in clusters 1 and 4. Furthermore, patients in cluster 2 (rate ratio [RR], 1.49; 95% confidence interval [CI], 1.16-1.92) and cluster 3 (RR, 1.61; 95% CI, 1.12-2.32) were at higher risk of exacerbation over a 12-month follow-up compared with cluster 1, even after adjustment for prior exacerbation history. Conclusions: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

Suicidal ideation and attempt among young people living in gosiwons in South Korea.

INTRODUCTION: Young people living in gosiwons could be at high risk for suicide owing to inadequate living conditions and the social stigma towards them. However, this topic has not received adequate academic attention. Gosiwon is a type of small residence consisting of several tiny rooms densely packed together and usually does not meet minimum housing standards. However, gosiwons are favored by low-income groups, especially young people, because they are cheaper than other residences. This study aimed to examine the factors that increase the risk of suicidal ideation and attempt among young people living in gosiwons. METHODS: A sample of 300 young people aged 19-34 years living in gosiwons for over 6 months was analyzed. A set of multinomial logistic regression was conducted to examine the factors that differentiate the suicidal ideation and attempt group from the no-suicidal risk group. RESULTS: Approximately 30% of the study participants experienced suicidal ideation or attempted suicide. Among several risk factors, social exclusion and depressive symptoms distinguished the group with suicidal ideation from the no-risk group. Depressive symptoms were the only factor that differentiated the group with suicide attempts history from the no-risk group. CONCLUSION: The results emphasize the need to focus on social exclusion and depressive symptoms among young people living in poor housing conditions. Interventions to address social exclusion and depressive symptoms may help prevent suicide risk among young people exposed to housing exclusion.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Tuberculosis and the Risk of Ischemic Heart Disease: A Nationwide Cohort Study.

BACKGROUND: Little is known about the risk of ischemic heart disease (IHD) in tuberculosis (TB) survivors. METHODS: We performed a population-based retrospective cohort study using the Korean National Health Insurance Service database. TB survivors (n = 60 602) and their 1:1 age- and sex-matched controls (n = 60 602) were enrolled. Eligible participants were followed up from 1 year after their TB diagnosis to the date of an IHD event, date of death, or the end of the study period (31 December 2018), whichever came first. The risk of IHD was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. Among IHD events, we additionally analyzed for myocardial infarction (MI). RESULTS: During a median of 3.9 years of follow-up, 2.7% of TB survivors (1633/60 602) and 2.0% of the matched controls (1228/60 602) developed IHD, and 0.6% of TB patients (341/60 602) and 0.4% of the matched controls (223/60 602) developed MI. The overall risk of developing IHD and MI was higher in TB patients (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI]: 1.12-1.32 for IHD and aHR 1.48, 95% CI: 1.23-1.78 for MI) than in the matched controls. Stratified analyses showed that TB survivors have an increased risk of IHD and MI regardless of income, place of residence, smoking status, alcohol consumption, physical activity, body mass index, and Charlson comorbidity index. CONCLUSIONS: TB survivors have a higher risk of IHD than matched controls. Strategies are needed to reduce the burden of IHD in TB survivors.

Long-Term Mortality of Tuberculosis Survivors in Korea: A Population-based Longitudinal Study.

BACKGROUND: When assessing long-term tuberculosis (TB) mortality, few studies addressed the impact of behavior habits and socioeconomic status. Therefore, we aimed to evaluate long-term TB mortality and risk factors while accounting for potential confounders. METHODS: This cohort study included TB survivors (n = 82 098) aged ≥20 years between 2010 and 2017, and 1:1 age- and sex-matched controls (n = 82 098). The participants were followed up for death 1 year after study enrollment until December 2018. Long-term mortality was adjusted for behavior habits (smoking, alcohol consumption, or exercise), income level, body mass index (BMI), and comorbidities. RESULTS: During a median of 3.7 years of follow-up, the incidence rate of mortality was significantly higher in TB survivors than those in the matched controls (18.2 vs. 8.8 per 1000 person-years, P < .001). Even after adjusting for potential confounders, the mortality risk was 1.62-fold (95% confidence interval [CI], 1.54-1.70) higher in TB survivors than those in the matched controls. In addition, the hazard of mortality in TB survivors relative to matched controls significantly increased in participants aged ≥30 years, with the highest risk in those in their 40s. Male sex (adjusted hazard ratio [HR]: 2.31; 95% CI, 2.16-2.47), smoking pack-years (HR: 1.005; 95% CI, 1.004-1.006), heavy alcohol consumption (HR: 1.12; 95% CI, 1.01-1.23), and lowest income (HR: 1.27; 95% CI, 1.18-1.37) were positively associated with increased hazards for mortality, whereas higher BMI (HR: 0.91; 95% CI, .90-.92) and regular exercise (HR: 0.82; 95% CI, .76-.88) reduced the hazards of long-term mortality in TB survivors. CONCLUSIONS: The long-term mortality risk was significantly higher in TB survivors than those in the matched controls, even after adjusting for potential confounders.

Increased Lung Cancer Risk and Associated Risk Factors in Tuberculosis Survivors: A Korean Population-Based Study.

BACKGROUND: Few studies have comprehensively evaluated the risk of lung cancer in tuberculosis survivors with consideration of smoking status and chronic obstructive pulmonary disease (COPD). Furthermore, little is known about lung cancer risk factors in tuberculosis survivors. METHODS: This population-based cohort study enrolled tuberculosis survivors (n = 75 467) between 2010 and 2017 and 1:1 age- and sex-matched controls. Subjects were followed up for 1 year from the date of tuberculosis diagnosis to the date of the incident lung cancer, death, or December 2018, whichever came first. The risk of lung cancer was evaluated according to smoking and COPD status. We also evaluated the risk factors for lung cancer and developed an individualized lung cancer prediction model for tuberculosis survivors. RESULTS: During a median follow-up duration of 4.8 years, the incident lung cancer risk was 1.72-fold higher in tuberculosis survivors than in the controls. Among tuberculosis survivors, those who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio, 6.78) compared with never-smoker, non-tuberculosis-infected controls. tuberculosis survivors with COPD had a higher risk (2.43) than non-COPD, non-tuberculosis-infected controls. Risk factors for lung cancer in tuberculosis survivors were pulmonary tuberculosis, age >60 years, smoking, and the presence of COPD or asthma. The individualized lung cancer risk model showed good discrimination (concordance statistic = 0.827). CONCLUSIONS: Previous tuberculosis infection is an independent risk factor regardless of smoking status or amount and COPD. Closer monitoring of tuberculosis survivors, especially heavy smokers or those with COPD, is needed for early lung cancer diagnosis.

Exploring horticultural traits and disease resistance in Capsicum baccatum through segmental introgression lines.

KEY MESSAGE: Segmental introgression and advanced backcross lines were developed and validated as important tools for improving agronomically important traits in pepper, offering improved sensitivity in detecting quantitative trait loci for breeding. Segmental introgression lines (SILs) and advanced backcross lines (ABs) can accelerate genetics and genomics research and breeding in crop plants. This study presents the development of a complete collection of SILs and ABs in pepper using Capsicum annuum cv. 'CM334' as the recipient parent and Capsicum baccatum 'PBC81', which displays various agronomically important traits including powdery mildew and anthracnose resistance, as donor parent. Using embryo rescue to overcome abortion in interspecific crosses, and marker-assisted selection with genotyping-in-thousands by sequencing (GT-seq) to develop SILs and ABs containing different segments of the C. baccatum genome, we obtained 63 SILs and 44 ABs, covering 94.8% of the C. baccatum genome. We characterized them for traits including powdery mildew resistance, anthracnose resistance, anthocyanin accumulation, trichome density, plant architecture, and fruit morphology. We validated previously known loci for these traits and discovered new sources of variation and quantitative trait loci (QTLs). A total of 15 QTLs were identified, including four for anthracnose resistance with three novel loci, seven for plant architecture, and four for fruit morphology. This is the first complete collection of pepper SILs and ABs validated for agronomic traits and will enhance QTL detection and serve as valuable breeding resources. Further, these SILs and ABs will be useful for comparative genomics and to better understand the genetic mechanisms underlying important agronomic traits in pepper, ultimately leading to improved crop productivity and sustainability.

Impact of Trimetazidine on the Incident Heart Failure After Coronary Artery Revascularization.

ABSTRACT: Abnormal myocardial metabolism is a common pathophysiological process underlying ischemic heart disease and heart failure (HF). Trimetazidine is an antianginal agent with a unique mechanism of action that regulates myocardial energy metabolism and might have a beneficial effect in preventing HF in patients undergoing myocardial revascularization. We aimed to evaluate the potential benefit of trimetazidine in preventing incident hospitalization for HF after myocardial revascularization. Using the common data model, we identified patients without prior HF undergoing myocardial revascularization from 8 hospital databases in Korea. To compare clinical outcomes using trimetazidine, database-level hazard ratios (HRs) were estimated using large-scale propensity score matching for each database and pooled using a random-effects model. The primary outcome was incident hospitalization for HF. The secondary outcome of interest was major adverse cardiac events (MACEs). After propensity score matching, 6724 and 11,211 patients were allocated to trimetazidine new-users and nonusers, respectively. There was no significant difference in the incidence of hospitalization for HF between the 2 groups (HR: 1.08, 95% confidence interval [CI], 0.88-1.31; P = 0.46). The risk of MACE also did not differ between the 2 groups (HR: 1.07, 95% CI, 0.98-1.16; P = 0.15). In conclusion, the use of trimetazidine did not reduce the risk of hospitalization for HF or MACE in patients undergoing myocardial revascularization. Therefore, the role of trimetazidine in contemporary clinical practice cannot be expanded beyond its current role as an add-on treatment for symptomatic angina.

Risk of Rapid Lung Function Decline in Young Adults With Chronic Obstructive Pulmonary Disease: A Community-Based Prospective Cohort Study.

It is unclear whether young adults with chronic obstructive pulmonary disease (COPD) are at an increased risk of rapid lung function decline. A total of 2,934 Korean adults aged 40-49 years who had consecutive lung function measurements were included. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity < lower limit of normal. The risk of rapid decline in FEV1, defined as ≥ 60 mL/year, was assessed using multivariable logistic regression analysis. In the multivariable model, a significantly higher risk of rapid decline in FEV1 was observed for the COPD group compared with the non-COPD group (adjusted odds ratio, 1.89; 95% confidence interval, 1.18-2.95), which was especially significant in subjects with FEV1 less than the median value (< 110%pred) (Pinteraction = 0.017) and inactive physical activity (Pinteraction = 0.039). In conclusion, the risk of rapid FEV1 decline was higher in young adults with COPD than in those without COPD, especially in those with FEV1 less than the median value and inactive physical activity.

Bioinformatics Analysis of Gene Expression Profiles for Diagnosing Sepsis and Risk Prediction in Patients with Sepsis.

: Although early recognition of sepsis is essential for timely treatment and can improve sepsis outcomes, no marker has demonstrated sufficient discriminatory power to diagnose sepsis. This study aimed to compare gene expression profiles between patients with sepsis and healthy volunteers to determine the accuracy of these profiles in diagnosing sepsis and to predict sepsis outcomes by combining bioinformatics data with molecular experiments and clinical information. We identified 422 differentially expressed genes (DEGs) between the sepsis and control groups, of which 93 immune-related DEGs were considered for further studies due to immune-related pathways being the most highly enriched. Key genes upregulated during sepsis, including S100A8, S100A9, and CR1, are responsible for cell cycle regulation and immune responses. Key downregulated genes, including CD79A, HLA-DQB2, PLD4, and CCR7, are responsible for immune responses. Furthermore, the key upregulated genes showed excellent to fair accuracy in diagnosing sepsis (area under the curve 0.747-0.931) and predicting in-hospital mortality (0.863-0.966) of patients with sepsis. In contrast, the key downregulated genes showed excellent accuracy in predicting mortality of patients with sepsis (0.918-0.961) but failed to effectively diagnosis sepsis.In conclusion, bioinformatics analysis identified key genes that may serve as biomarkers for diagnosing sepsis and predicting outcomes among patients with sepsis.

Association between non-cystic fibrosis bronchiectasis and the risk of incident dementia: A nationwide cohort study.

BACKGROUND: Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. OBJECTIVES: To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. METHODS: A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer's disease and vascular dementia. RESULTS: During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p < .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04-1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer's disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01-1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90-1.21). CONCLUSION: Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer's disease.

Female Reproductive Factors and Incidence of Nontuberculous Mycobacterial Pulmonary Disease Among Postmenopausal Women in Korea.

BACKGROUND: There are conflicting results regarding endogenous estrogen exposure and risk of incident nontuberculous mycobacterial pulmonary disease (NTM-PD). In addition, evidence on impact of hormone replacement therapy (HRT) on risk of NTM-PD is lacking. This study aimed to evaluate the impacts of endogenous estrogen exposure and HRT on risk of NTM-PD in postmenopausal women. METHODS: This population-based cohort study comprised 1 400 095 postmenopausal women without previous NTM-PD who participated in the 2009 national health screening exam in South Korea. The cohort was followed until the date of incident NTM-PD, death, or December 2018. We evaluated whether lifetime endogenous estrogen exposure and HRT were associated with incident NTM-PD. Endogenous estrogen exposure was evaluated using age at menarche and menopause and reproductive period (duration between age at menarche and age at menopause). RESULTS: During a median of 8.4 (interquartile range, 8.2-8.7) years of follow-up, 0.1% of participants (1818/1 400 095) developed NTM-PD, with an incidence rate of 0.15/1000 person-years. Multivariable Cox regression analyses showed no significant relationship between endogenous estrogen exposure (age at menarche, age at menopause, and reproductive period) and risk of NTM-PD. In contrast, duration of HRT showed a significant dose-response relationship with incident NTM-PD even after adjustment for demographics and reproductive factors (adjusted hazard ratio [95% CI]: 1.30 [1.12-1.51] in HRT for <2 years; 1.28 [1.03-1.59] in 2-5 years; and 1.65 [1.33-2.05] in ≥5 years). CONCLUSIONS: While there was no significant association with endogenous estrogen exposure, HRT was monotonically associated with increased risk of NTM-PD in postmenopausal women.

Tuberculosis and Risk of Ischemic Stroke: A Nationwide Cohort Study.

BACKGROUND: Conflicting results exist regarding the risk of ischemic stroke in tuberculosis survivors. We aimed to estimate the risk of ischemic stroke using a nationwide population-based retrospective cohort. METHODS: We gathered data from the Korean National Health Insurance Service on tuberculosis survivors and 1:1 age- and sex-matched non-tuberculosis cases. Eligible participants were followed up from 1 year after tuberculosis diagnosis to the date of ischemic stroke event, date of death, or until the end of the study period (December 31, 2018), whichever came first. Cox proportional hazard regression and stratified analyses were performed to identify any related factors. RESULTS: During follow-up periods of 3.8 years for patients with tuberculosis and matched non-tuberculosis cases, 1.3% of patients with tuberculosis (941/72 863) and 1.0% of matched non-tuberculosis cases (707/72 863) developed ischemic stroke. The overall risk of ischemic stroke was higher in tuberculosis patients (adjusted hazard ratio: 1.22 [95% CI, 1.10-1.36]) compared with the matched non-tuberculosis cases. A stratified analysis showed that patients with tuberculosis had increased risk of ischemic stroke regardless of age, sex, smoking status, alcohol consumption, physical activity, body mass index, and Charlson Comorbidity Index score. CONCLUSIONS: Tuberculosis survivors had a higher risk of ischemic stroke than their matched non-tuberculosis cases. The results of this study suggest that tuberculosis is a crucial infectious factor associated with increased incidence of ischemic stroke.

Association between exercise and risk of cardiovascular diseases in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Although cardiovascular comorbidities negatively impact survival in patients with bronchiectasis, there is limited evidence to recommend exercise in this population. We aimed to evaluate whether exercise habit changes are related to reduced cardiovascular disease risk and explore an optimal exercise amount. METHODS: This study identified 165,842 patients with newly diagnosed bronchiectasis during 2010-2016 who underwent two health examinations and were followed up until December 2020. The exposure was the change in weekly habits of moderate- or vigorous-intensity physical activity between the two examinations, classified into non-exercisers and exercisers (further classified into new exercisers, exercise dropouts, and exercise maintainers). The amount of exercise was measured using metabolic equivalents of task (MET). The outcome was the incidence of myocardial infarction (MI) or stroke. RESULTS: During a mean of 6.2 ± 2.1 follow-up years, 4,233 (2.6%) and 3,745 (2.3%) of patients with bronchiectasis had MI or stroke, respectively. Compared to non-exercisers, exercisers had a significantly lower risk of MI or stroke by 9-28% (p < 0.001 for both). Among exercisers, exercise maintainers showed the lowest risk of MI (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.64-0.81) and stroke (aHR, 0.72; 95% CI, 0.64-0.82) compared to non-exercisers. Regarding exercise amount, a significant risk reduction was observed only in patients with bronchiectasis who exercised for ≥ 500 MET-min/wk. CONCLUSION: Exercise was associated with a reduced risk of cardiovascular diseases in patients with bronchiectasis. In particular, the risk was lowest in exercise maintainers, and cardiovascular risk reduction was significant when exercising more than 500 MET-min/wk.

Incidence and outcomes of adverse drug reactions to first-line anti-tuberculosis drugs and their effects on the quality of life: A multicenter prospective cohort study.

BACKGROUND: In tuberculosis (TB) treatment, adverse drug reactions (ADRs) can interrupt treatment and decrease the quality of life (QoL). We aimed to prospectively investigate the incidence of ADRs to first-line anti-TB drugs and related outcomes and QoL. METHODS: Adult patients with TB who had been treated with first-line anti-TB drugs in five Korean hospitals were enrolled. ADR questionnaire surveys and blood tests were performed four times serially, and QoL was assessed on the fourth TB treatment week (±2 weeks). RESULTS: Of 410 enrolled patients with TB (males, 62%; mean age, 52.1 ± 18.1 years [those aged ≥65 years, 26.6%]), 67.8% experienced any ADRs (≥ grade 2) to TB drugs. The most common ADR was fatigue (53.2%), followed by itching (42.7%) and anorexia (41.7%). Older adult patients experienced relatively more ADRs, including anorexia, dyspepsia, rash, dizziness, anemia, abnormal hepatic/renal function tests, and increased uric acid levels (p < 0.05). Treatment regimens changed for 9.5% of patients owing to ADRs to anti-TB drugs. Patients with any ADRs and older adult patients had significantly lower QoL than their counterparts (p < 0.05). Old age (odds ratio [OR], 1.02) and being male (OR 2.65) were independently associated with ADRs, whereas active smoking (OR 4.73) and a relatively long treatment phase (OR 5.13) were independently associated with hepatotoxicity. CONCLUSION: ADRs to first-line anti-TB drugs were common and related to relatively low QoL, especially among older adults. Although 9.5% of patients had ADR-related regimen changes, most patients with ADRs completed treatments successfully.

Chronic Obstructive Pulmonary Disease is Associated with a More Symptomatic Burden and Severe Presentation of COVID-19: A Korean National COVID-19 Cohort Study.

Insufficient data are available on comprehensive evaluation of demographics, symptoms or signs, laboratory findings, and disease course in patients with coronavirus disease 2019 (COVID-19) and chronic obstructive pulmonary disease (COPD). We aimed to evaluate whether COPD patients are more prone to severe COVID-19 compared with those without COPD. We also investigate the clinical characteristics and disease course of COVID-19 in patients with COPD versus those without COPD. Patients were selected from a Korean nationwide cohort of 5,628 patients with confirmed COVID-19 and who had completed treatment or quarantine by April 30, 2020; 3,673 patients aged 40 years or older were included in this study. COPD was diagnosed using patient reports of physician-diagnosed COPD. During the study period, all patients with COVID-19 in Korea were hospitalized following the national health policy. Of the study participants, 38 (1.0%) had COPD. Regarding initial symptoms, COPD patients with COVID-19 showed greater sputum production (50.0% vs. 29.8%, p < 0.01) and dyspnea (36.8% vs. 14.9%, p < 0.01) than those without COPD. In addition, patients with COPD were more likely to receive oxygen therapy or non-invasive ventilation (29.0% vs. 13.7%, p = 0.01) and had a higher mortality (21.1% vs. 6.4%, p < 0.01) than those without COPD. After adjusting for age, sex, body mass index, and comorbidities, COPD patients showed increased risk of severe COVID-19 compared with those without COPD. Our nationwide study showed that COVID-19 patients with COPD have higher symptomatic burden and more severe disease course than those without COPD.