Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Characteristics of subclinical tuberculosis compared to active symptomatic tuberculosis using nationwide registry cohort in Korea: prospective cohort study.

Objective: The clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis challenging. To improve our understanding of the disease progression mechanism, we aimed to identify the characteristics of subclinical TB and important predictors of symptom development. Methods: From July 2018 to June 2019, we systemically collected data from the National Surveillance System of South Korea on patients with pulmonary TB, and compared the characteristics of subclinical and active symptomatic TB patients. Results: A total of 4,636 patients with pulmonary TB were included, and the prevalence of subclinical TB was 37.1% (1,720/4,636). In subclinical TB patients, the positivity rates of acid-fast bacilli (AFB) smear and culture were 16.2 and 50.2%, respectively. Subclinical TB patients were younger (55.6 ± 19.2 vs. 60.7 ± 19.5, P < 0.001), had a higher body mass index (21.7 ± 3.1 vs. 21.0 ± 3.5, P < 0.001), less under Medicaid support, and had lower rates of chronic lung disease, AFB smear and culture positivity, and bilateral disease. Regarding the characteristic differences of individual TB-related symptoms, age was positively associated with dyspnoea and general weakness but negatively associated with chest pain, haemoptysis, and weight loss. Male patients were more prone to weight loss. Chronic lung disease was related to symptoms including cough/phlegm, dyspnoea, and haemoptysis, while autoimmune diseases were associated with fever and weight loss. Conclusions: The development of TB-related symptoms was associated with microbiological burden and clinical characteristics including underlying comorbidities, which should be evaluated carefully.

Risk of loss to follow-up among tuberculosis patients in South Korea: whom should we focus on?

Introduction: In South Korea, public-private mix (PPM) has been a key strategy in national tuberculosis (TB) control program. This study aimed to identify rate of loss to follow-up (LTFU) among TB patients in nationwide PPM institutions and their risk factors. Methods: A nationwide prospective observational study including drug susceptible TB patients diagnosed from the 1st day to the 10th day of every month between July 2018 and December 2020 in PPM institutions was designed. Multivariable survival models in which death and failure were designated as events with competing risk were used to investigate risk factors for LTFU. Results: A total of 14,942 patients were included. Of them, 356 (2.4%) had an LTFU. Risk factors for LTFU were: underweight patients (adjusted hazard ratio (aHR): 1.47, 95% CI: 1.12-1.92), patients living alone (aHR: 1.43, 95% CI: 1.16-1.76), heavy drinkers (aHR: 1.67, 95% CI: 1.16-2.39), those with malignancy (aHR: 1.49, 95% CI: 1.07-2.05), foreigners (aHR: 5.96, 95% CI: 4.51-7.89), and those with previous TB history reported as an unfavorable outcome (aHR: 4.43, 95% CI: 2.77-7.08). Effect of age on LTFU was not significant. Brief interruption of anti-TB treatment (less than two months) in current session was associated with subsequent LTFU [adjusted odds ratio: 13.09 (10.29-16.66)]. Conclusion: Identifying vulnerability of patients such as living alone, being heavy alcoholics, being foreigners or having previous TB history reported as an unfavorable outcome is required. Thorough case management for these vulnerable groups could be feasible with collaboration between public and private sectors.

Effects of underweight and overweight on mortality in patients with pulmonary tuberculosis.

Background: Poor nutrition increases disease severity and mortality in patients with tuberculosis (TB). There are gaps in our understanding of the effects of being underweight or overweight on TB in relation to sex. Methods: We generated a nationwide TB registry database and assessed the effects of body mass index (BMI) on mortality in patients with pulmonary TB. The cause of death was further classified as TB-related or non-TB-related deaths. First, logistic regression analysis was performed to assess the association between BMI (a continuous variable) and mortality, and subgroup analyses of the multivariable logistic regression model were performed separately in male and female patients. Second, we categorized BMI into three groups: underweight, normal weight, and overweight, and assessed the impact of being underweight or overweight on mortality with reference to normal weight. Results: Among 9,721 patients with pulmonary TB, the mean BMI was 21.3 ± 3.4; 1,927 (19.8%) were underweight, and 2,829 (29.1%) were overweight. In multivariable logistic regression analysis, mortality was significantly increased with the decrement of BMI (adjusted odds ratio [aOR] = 0.893, 95% confidence interval [CI] = 0.875-0.911). In subgroup analyses, underweight patients had significantly higher odds of mortality, especially TB-related deaths (aOR = 2.057, 95% CI = 1.546-2.735). The association with mortality and male patients was higher (aOR = 2.078, 95% CI = 1.717-2.514), compared with female patients (aOR = 1.724, 95% CI = 1.332-2.231). Being overweight had a significant protective effect against TB-related death only in females (aOR = 0.500, 95% CI = 0.268-0.934), whereas its effect on non-TB-related death was observed only in males (aOR = 0.739, 95% CI = 0.587-0.930). Conclusion: Being underweight was linked to high mortality, whereas being overweight had beneficial effects in patients with pulmonary TB.

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea.

Background: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT. Methods: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated. Results: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders. Conclusions: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

Deaths from tuberculosis: differences between tuberculosis-related and non-tuberculosis-related deaths.

Objective: Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide. The first step in developing strategies to reduce TB mortality is to identify the direct causes of death in patients with TB and the risk factors for each cause. Methods: Data on patients with TB systemically collected from the National Surveillance System of South Korea from January 2019 to December 2020 were included in this study. We analyzed the clinical characteristics associated with TB and non-TB-related deaths, including TB-related symptoms, comorbidities, and radiographic and microbiological findings. Results: Of the total of 12,340 patients with TB, 61% were males with a mean age of 61.3 years. During the follow-up period, the overall mortality rate was 10.6%, with TB-related deaths accounting for 21.3% of all TB deaths. The median survival time in the TB-related death group was 22 days. TB-related death was associated with older age, lower body mass index (BMI), dyspnea, fever, general weakness, bilateral radiographic patterns, and acid-fast bacilli (AFB)-positive smears. Non-TB-related deaths were associated with older age, male sex, lower BMI, comorbidities of heart, liver, kidney, and central nervous system (CNS) diseases, CNS TB involvement, the presence of dyspnea, general weakness, and bilateral radiographic patterns. Conclusion: Patients with high-risk TB must be identified through cause-specific mortality analysis, and the mortality rate must be reduced through intensive monitoring of patients with a high TB burden and comorbidities.

Delphi Survey on the Current and Future Korean Guidelines for Isoniazid-Monoresistant Tuberculosis.

Purpose: Isoniazid-monoresistant tuberculosis (Hr-TB) has emerged as a global challenge, necessitating detailed guidelines for its diagnosis and treatment. We aim to consolidate the Korean guidelines for Hr-TB management by gathering expert opinions and reaching a consensus. Patients and Methods: A conventional Delphi method involving two rounds of surveys was conducted with 96 experts selected based on their clinical and research experience and involvement in nationwide tuberculosis studies and development of the Korean guidelines on tuberculosis. The survey consisted of three sections of questionnaires on diagnosis, treatment, and general opinions on Hr-TB. Results: Among the 96 experts, 72 (75%) participated in the two rounds of the survey. A majority of experts (96%) strongly agreed on the necessity of molecular drug susceptibility testing (DST) for isoniazid and rifampin resistance in all tuberculosis patients and emphasized the importance of interpreting mutation types (inhA or katG) and additional molecular DST for fluoroquinolones for confirmed isoniazid-resistant cases. Over 95.8% of experts recommended treating Hr-TB with a combination of rifampin, ethambutol, pyrazinamide, and levofloxacin for six months, without exceeding 12 months unless necessary. They also acknowledged the drawbacks of long-term pyrazinamide use due to its side effects and agreed on shortening its duration by extending the duration of the rest of the treatment with a modified combination of choice. Conclusion: This Delphi survey enabled Korean tuberculosis experts to reach a consensus on diagnosing and treating Hr-TB. These findings will be valuable for developing the upcoming revised Korean guidelines for Hr-TB management.

High urinary desmosine is associated with long-term mortality in patients with COPD.

COPD patients with high baseline urinary desmosines demonstrated significantly higher mortality than those with lower urinary desmosines. High urinary desmosine is independently associated with an increased risk of long-term mortality in COPD patients. https://bit.ly/4015xZ9.

Recommendation of pharmacokinetics/pharmacodynamics target of ethambutol to suppress tuberculosis resistance: A population pharmacokinetics study on a large prospective cohort.

BACKGROUND: The ability of ethambutol (EMB) to suppress bacterial resistance has been demonstrated in a time-dependent manner. Through the development of a population pharmacokinetics (PK) model, this study aimed to suggest the PK/pharmacodynamics (PD) target and identify the significant covariates that influence interindividual variability (IIV) in the PK of EMB. METHODS: In total, 837 patients from 20 medical centres across Korea were enrolled in this study. The non-linear mixed-effect method was used to establish and validate the population PK model. RESULTS: A two-compartment model with transit compartment absorption was sufficient to describe the PK of EMB. Body weight and renal function were identified as significant covariates that affect IIV of the apparent clearance (CL/F) of EMB. Patients with moderate renal function showed 35% and 55% lower CL/F (CL/F 89.9 L/h) compared with those with mild and normal renal function, respectively. All the renal function groups with simulated doses ranging from 800 to 1200 mg achieved area under the curve over minimum inhibitory concentration (MIC) >119, and maintained T>MIC for >23 h for MIC of 0.5 µg/mL. Based on our simulation result, it is suggested that doses of 800, 1000, and 1200 mg should obtain the T>MIC target of 4, 6, and 8 h, respectively. This model was validated internally and externally. CONCLUSION: This study provides insight into the PK/PD indexes of EMB for three different renal function groups and T>MIC targets for different doses. The results could be used to provide optimal-dose suggestions for EMB.

Differential effects of sex on tuberculosis location and severity across the lifespan.

Disparities exist between sexes regarding tuberculosis (TB) incidence, as well as disease severity and outcome. Using a nationwide TB registry database, we explored the impact of sex and age on extrapulmonary TB (EPTB) among all enrolled patients by (1) calculating the female proportion for every age category according to TB-affected locations, (2) calculating the proportions of EPTB stratified by sex according to age, (3) conducting multivariable analysis to examine the impact of sex and age on EPTB likelihood, and (4) assessing the odds of EPTB for female compared to male as reference in every age category. Further, we explored the impact of sex and age on disease severity among pulmonary TB (PTB) patients. Of all the TB patients, 40.1% were female, with a male-to-female ratio of 1.49. The proportion of females was lowest in their fifties, resembling a U-shape. The male-to-female ratios in PTB and EPTB were 1.67 and 1.03, respectively. Compared to men, women were significantly associated with EPTB in their forties, fifties, and sixties. Female patients with PTB had significantly lower odds of having cavitation and positive smear test results in their fifties. Significant differences were found concerning TB location and severity between sexes, especially during reproductive age.

Chronic Hypoxemia Triggers a Neuropathic Process in Chronic Obstructive Pulmonary Disease: Insight From In Vivo Neurophysiological Assessments.

BACKGROUND AND PURPOSE: Peripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. METHODS: The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength-duration time constant, threshold electrotonus (TE), current-threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). RESULTS: In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40-60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. CONCLUSIONS: The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+-K+-ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

Two cases of large tracheobronchial schwannomas completely resected by rigid bronchoscopy with multiple instruments.

Primary tracheobronchial schwannomas are extremely rare. Surgical treatment has been the first choice for these benign tumours due to the substantial residual rates and recurrences after bronchoscopic resection. In addition, there has been limited information on bronchoscopic removal of endobronchial schwannomas. We describe two cases of large tracheal and bronchial schwannomas that were completely and successfully resected by snare electrocautery, insulation-tipped knife, and argon plasma coagulation under rigid bronchoscopy. These cases highlight that rigid bronchoscopic treatment with these multiple instruments can be a good treatment option for endotracheal or endobronchial schwannomas.

Trends and an Online Survey on the Use of Rigid Bronchoscopy in Korea.

BACKGROUND: Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. METHODS: We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. RESULTS: While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003-2005 to 468 in 2018-2020, that of other institutions increased from 0 to 238. The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%. The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, rs = -0.740, P = 0.003) and recent administrative difficulties were encountered (rs = -0.616, P = 0.019). CONCLUSION: This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

Association of Underlying Comorbidities and Sites of tuberculosis: an analysis using surveillance data.

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.

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.

Time delays and risk factors in the management of patients with active pulmonary tuberculosis: nationwide cohort study.

Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0-40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639-2.687; p < 0.001] and heavy alcohol intake (adjusted OR 1.505; 95% CI 1.187-1.907; p < 0.001). The median healthcare delay was 5.0 (1.0-14.0) days. A longer healthcare delay was associated with malignancy (adjusted OR 1.351; 95% CI 1.069-1.709; p = 0.012), autoimmune disease (adjusted OR 2.445; 95% CI 1.295-4.617; p = 0.006), and low bacterial burden manifested as an acid-fast bacillus smear-negative and tuberculosis polymerase chain reaction-negative status (adjusted OR 1.316; 95% CI 1.104-1.569; p = 0.002). Active case-finding programmes need to focus on patients with heavy alcoholism or neuropsychiatric diseases. To ensure early PTB detection, healthcare providers must carefully monitor patients with malignancy, autoimmune disease, or a high index of suspicion for PTB.

Cluster analysis categorizes five phenotypes of pulmonary tuberculosis.

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.