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Abstract Background Despite a well-known relation between smoking tobacco and the tuberculosis epidemic, the factors associated with smoking cessation in tuberculosis patients are unclear. This study aims to examine the cascade of smoking cessation and the factors associated with persistent smoking among tuberculosis patients. Methods We conducted a prospective cohort study enrolling adult patients with pulmonary tuberculosis between 2016 and 2019 in the Republic of Korea. We examined the smoking status at baseline, followed the current smokers, re-examined their smoking status after 6 months of anti-tuberculosis treatment, and identified the factors associated with persistent smoking. Results Of the 419 enrolled patients, 109 (26.0%) were current smokers at baseline. Of the 79 current smokers who completed the 6-month survey, 24 (30.4%) succeeded in quitting smoking after 6 months of treatment. The adjusted odds ratio for persistent smoking was 6.57 (95% confidence interval [CI], 1.76–27.83) for drinking and 0.15 (95% CI, 0.03–0.68) for diabetes comorbidity. Conclusion Drinking alcohol and diabetes comorbidity were important factors in smoking cessation. Only one third of the tuberculosis patients in our study cohort succeeded in quitting smoking during the 6-month treatment period. More aggressive interventions for smoking cessation should be adopted within the national anti-tuberculosis program.

Abstract Background The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. Methods Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. Results Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. Conclusions Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. Trial registration This study registered ClinicalTrials.gov NO. NCT05280886.

Abstract Background Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site. Methods We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB. Results A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52–4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08–6.99). Conclusions We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.

Abstract Background Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. We aimed to describe the clinical and laboratory findings of subclinical disease among pulmonary TB patients and compared treatment outcomes for subclinical and active diseases. Methods In this prospective cohort study, we enrolled adult patients aged ≥ 19 years with pulmonary TB between 2016 and 2018. Subclinical TB was defined as radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented a two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active diseases using multivariable binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort. Results Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariable analysis showed that age

Abstract Background To improve treatment outcomes for tuberculosis (TB), efforts to reduce treatment failure are necessary. The aim of our study was to describe the characteristics of subjects who had failed treatment of tuberculosis and identify the risk factors for treatment failure and poor compliance using national data. Methods A multicenter cross-sectional study was performed on tuberculosis subjects whose final outcome was reported as treatment failure during 2015–2017. The same number of subjects with treatment success during the same study period were randomly selected for comparison. Demographics, microbiological, radiographic, and clinical data were collected based on in-depth interviews by TB nurse specialists at all Public Private Mix (PPM) participating hospitals in South Korea. Results A total of 52 tuberculosis patients with treatment failure were enrolled. In a multivariable analysis, the presence of diabetes, previous history of tuberculosis, and cavity were identified as risk factors for treatment failure; and Medicaid support was a favorable factor for treatment success (area under the curve [AUC]: 0.79). Age, low body mass index (BMI), presence of diabetes, preexisting lung disease, positive sputum acid-fast bacilli (AFB) smear result, and the presence of multidrug-resistant tuberculosis (MDR-TB) were significantly associated with presence of cavities. Younger age, lower BMI and previous history of TB were associated with poor compliance during treatment (AUC: 0.76). Conclusion To reduce treatment failure, careful evaluation of the presence of diabetes, previous TB history, underlying lung disease, cavity, results of sputum AFB smears, and socioeconomic status are needed. To enhance treatment compliance, more attention should be paid to younger patients with lower BMIs during follow-up.

Abstract Background The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. Methods Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed. Results Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. Conclusions The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.

Abstract Background Although the incidence of tuberculosis (TB) has decreased in South Korea, the mortality rate remains high. TB mortality is a key indicator for TB control interventions. The purpose of this study was to assess early and TB-related mortality during anti-TB treatment and describe the associated clinical characteristics. Methods A multicenter cross-sectional study was performed across South Korea. Patients with pulmonary TB who died during anti-TB treatment and whose records were submitted to the national TB surveillance system between 2015 and 2017 were enrolled. All TB deaths were categorized based on cause (TB-related or non-TB-related) and timing (early or late). We identified statistical associations using the frequency table, chi-square test, and binary logistic regression. Results Of 5595 notifiable mortality cases, 3735 patients with pulmonary TB were included in the analysis. There were 2541 (68.0%) male patients, and 2935 (78.6%) mortality cases were observed in patients older than 65 years. There were 944 (25.3%) cases of TB-related death and 2545 (68.1%) cases of early death. Of all cases, 187 (5.0%) patients were diagnosed post-mortem and 38 (1.0%) patients died on the first day of treatment. Low body mass index (adjusted odds ratio (aOR) = 1.26; 95% confidence interval (CI) = 1.08–1.48), no reported illness (aOR = 1.36; 95% CI = 1.10–1.68), bilateral disease on chest X-ray (aOR = 1.30; 95% CI = 1.11–1.52), and positive acid-fast bacilli smear result (aOR = 1.30; 95% CI = 1.11–1.52) were significantly associated with early death, as well as TB-related death. Acute respiratory failure was the most common mode of non-TB-related death. Malignancy was associated with both late (aOR = 0.71; 95% CI = 0.59–0.89) and non-TB-related (aOR = 0.35; 95% CI = 0.26–0.46) death. Conclusions A high proportion of TB death was observed in elderly patients and attributed to non-TB-related causes. Many TB-related deaths occurred during the intensive phase, particularly within the first month. Further studies identifying risk factors for different causes of TB death at different phases of anti-TB treatment are warranted for early targeted intervention in order to reduce TB mortality.