Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Clinical course of nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis.

OBJECTIVES: The impact of rheumatoid arthritis (RA) on nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been well established. In this study, we investigated the clinical course of NTM-PD in patients with RA and the impact of RA on the prognosis of NTM-PD. METHODS: We analyzed patients who developed NTM-PD after being diagnosed with RA from January 2004 to August 2023 at a tertiary referral hospital in South Korea. The patient's baseline characteristics, clinical course, and prognosis were evaluated. An optimal matching analysis was performed to measure the impact of RA on the risk of mortality. RESULTS: During the study period, 18 patients with RA [median age, 68 years; interquartile range (IQR) 59-73; female, 88.9%] developed NTM-PD. The median interval between RA diagnosis and subsequent NTM-PD development was 14.8 years (IQR, 8.6-19.5). At a median of 30 months (IQR, 27-105) after NTM-PD diagnosis, 10 of 18 (55.6%) patients received anti-mycobacterial treatment for NTM-PD and 5 (50.0%) patients achieved microbiological cure. When matched to patients with NTM-PD but without RA, patients with both RA and NTM-PD had a higher risk of mortality (adjusted hazard ratio, 8.14; 95% confidence interval, 2.43-27.2). CONCLUSION: NTM-PD occurring after RA is associated with a higher risk of mortality than NTM-PD in the absence of RA.

Rates and Risk Factors of Progression in Patients With Nontuberculous Mycobacterial Pulmonary Disease: Secondary Analysis of a Prospective Cohort Study.

BACKGROUND: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. RESEARCH QUESTION: What is the rate of NTM-PD progression, and what are the predictors of progression? STUDY DESIGN AND METHODS: Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. RESULTS: Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression. INTERPRETATION: About half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01616745; URL: www. CLINICALTRIALS: gov.

Treatment Outcomes of Clofazimine-Containing Regimens in Severe Mycobacterium avium Complex Pulmonary Disease.

Background: Clofazimine is suggested as a promising drug for the treatment of nontuberculous mycobacterial pulmonary disease. However, the role of clofazimine in severe Mycobacterium avium complex pulmonary disease (MAC-PD) remains unclear. In this study, we investigated the treatment outcomes of patients with severe MAC-PD treated with regimens containing clofazimine. Methods: This study included patients diagnosed with severe MAC-PD at Seoul National University Hospital who underwent anti-mycobacterial treatment between 1 January 2011 and 31 December 2022. We assessed the rate of culture conversion within 6 months and microbiological cure in patients receiving clofazimine-containing regimens, considering the dose and duration of clofazimine administration. Results: A total of 170 patients with severe MAC-PD, treated with regimens containing clofazimine, were included in the analysis. The median age of patients was 68 years (interquartile range, 59-75 years), with a female predominance (n = 114 [67.1%]). Cavities were identified in 121 patients (71.2%). Within 6 months, 77 patients (45.3%) achieved culture conversion, and 84 of 154 (54.6%) patients attained microbiological cure. The dose of clofazimine (100 mg vs 50 mg) was not associated with culture conversion (adjusted odds ratio [aOR], 0.64 [95% confidence interval {CI}, .29-1.42]) or microbiological cure (aOR, 1.21 [95% CI, .52-2.81]). The microbiological cure rate reached 71.0% when clofazimine was administered for 6-12 months, compared to 23.1% when administered for <6 months. Conclusions: Clofazimine demonstrated a relatively favorable efficacy in severe MAC-PD, regardless of the maintenance dose. This effect was more pronounced when administered for a duration exceeding 6 months.

Metabolomic Characteristics of Nontuberculous Mycobacterial Pulmonary Disease.

BACKGROUND: The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD-specific metabolic pathways using serum metabolomics to understand disease pathogenesis. METHODS: Mass spectrometry-based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling. RESULTS: Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group. CONCLUSION: In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches.

The Impact of Trehalose Dimycolate on the Clinical Course of Mycobacterium avium Complex Pulmonary Disease.

Rationale The clinical implications of trehalose 6,6'-dimycolate (TDM) in nontuberculous mycobacterial pulmonary disease have not been studied. Objective To examine the presence of TDM in clinical isolates obtained from patients with Mycobacterium avium complex (MAC) pulmonary disease (PD) and its impact on disease severity and treatment outcomes. Methods We analyzed clinical isolates from patients diagnosed with MAC-PD at Seoul National University Hospital between January 1, 2019, and December 31, 2021. The lipids were extracted from clinical isolates obtained at the time of diagnosis using mass spectrometry. Mass peaks between 300 and 3,500 m/z were obtained, and the peak patterns of the total lipids were analyzed. Results TDMs were identified in clinical isolates from 176 out of 343 patients. Cavities were more prevalent in patients with TDM-negative isolates (19.8%) than in patients with TDM-positive isolates (10.2%) (P=0.015). The time to antibiotic treatment was shorter in patients with TDM-negative isolates (4 months, interquartile range [IQR] 2-10) than in patients with TDM-positive isolates (7 months, IQR 3-16, P=0.032). Patients with TDM-negative isolates had a significantly lower proportion of culture conversions (P=0.012). TDM was associated with higher likelihood of culture conversion (adjusted hazard ratio, 2.29; P=0.035). Conclusions TDM-negative isolates were linked to a higher occurrence of cavities, earlier initiation of treatment, and worse treatment outcome in MAC-PD patients.

Post-treatment Radiographic Severity and Mortality in Mycobacterium avium Complex Pulmonary Disease.

Rationale: Imaging studies are widely performed when treating Mycobacterium avium complex pulmonary disease (MAC-PD); however, the clinical significance of post-treatment radiographic change is unknown. Objectives: To determine whether a deep neural network trained with pulmonary tuberculosis could adequately score the radiographic severity of MAC-PD and then to examine relationships between post-treatment radiographic severity and its change from baseline and long-term prognosis. Methods: We retrospectively collected chest radiographs of adult patients with MAC-PD treated for ⩾6 months at baseline and at 3, 6, 9, and 12 months of treatment. We correlated the radiographic severity score generated by a deep neural network with visual and clinical severity as determined by radiologists and mycobacterial culture status, respectively. The associations between the score, improvement from baseline, and mortality were analyzed using Cox proportional hazards regression. Results: In total, 342 and 120 patients were included in the derivation and validation cohorts, respectively. The network's severity score correlated with radiologists' grading (Spearman coefficient, 0.40) and mycobacterial culture results (odds ratio, 1.02; 95% confidence interval [CI], 1.0-1.05). A significant decreasing trend in the severity score was observed over time (P < 0.001). A higher score at 12 months of treatment was independently associated with higher mortality (adjusted hazard ratio, 1.07; 95% CI, 1.03-1.10). Improvements in radiographic scores from baseline were associated with reduced mortality, regardless of culture conversion (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.80). These findings were replicated in the validation cohort. Conclusions: Post-treatment radiographic severity and improvement from baseline in patients with MAC-PD were associated with long-term survival.

Genetic stability of Mycobacterium abscessus during antibiotic treatment.

OBJECTIVES: Genetic changes in Mycobacterium abscessus during antibiotic treatment are not fully understood. This study aimed to investigate the genetic changes in M. abscessus in patients receiving antibiotic treatment, and their clinical implications. METHODS: Pretreatment and 12-month post-treatment M. abscessus isolates were obtained from patients with M. abscessus pulmonary disease. Isolates from each time point were separated into six groups based on their distinctive morphological characteristics. Twenty-four isolates, comprising 12 from patient A exhibiting progressive disease and 12 from patient B demonstrating stable disease, underwent sequencing. Subsequently, minimal inhibitory concentrations (MICs) for the administered antibiotics were measured. RESULTS: Persistent infection with a single strain was observed in patients A and B. During 12 months of treatment, MICs for administered drugs did not generally change over time in either patient and single nucleotide variations (SNV) associated with antimicrobial resistance (rrl, rrs, erm(41), gyrA, gyrB, whiB7 and hflX) were not mutated. Although not significant, 47 and 52 non-synonymous SNVs occurred in M. abscessus from patients A and B, respectively, and the accumulation of these SNVs differed in patients A and B, except for five SNVs. The most variable positions were within a probable NADH-dependent glutamate synthase gene and a putative YrbE family protein gene in patients A and B, respectively. CONCLUSIONS: Persistent infections by a single strain of M. abscessus were observed in two patients with different clinical courses. Genetic changes in M. abscessus during antibiotic treatment were relatively stable in these patients. CLINICAL TRIALS IDENTIFIER: NCT01616745 (ClinicalTrials.gov ID).

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.

Microbiological Cure at Treatment Completion Is Associated With Longer Survival in Patients With Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Morbidity and mortality from nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing. Mycobacterium avium complex (MAC) is the most common cause of NTM-PD. Microbiological outcomes are widely used as the primary end point of antimicrobial treatment, but their long-term impact on prognosis is uncertain. RESEARCH QUESTION: Do patients who achieve microbiological cure at the end of treatment have longer survival than those who do not? STUDY DESIGN AND METHODS: We retrospectively analyzed adult patients who met the diagnostic criteria for NTM-PD, were infected with MAC species, and were treated with a macrolide-based regimen for ≥ 12 months per guidelines between January 2008 and May 2021 at a tertiary referral center. Mycobacterial culture was performed during antimicrobial treatment to assess the microbiological outcome. Patients with three or more consecutive negative cultures collected ≥ 4 weeks apart and no positive cultures until treatment completion were considered to have achieved microbiological cure. To assess the impact of microbiological cure on all-cause mortality, we performed multivariable Cox proportional hazards regression analysis adjusted for age, sex, BMI, presence of cavitary lesions, erythrocyte sedimentation rate, and underlying comorbid conditions. RESULTS: Among 382 patients enrolled, 236 (61.8%) achieved microbiological cure at completion of treatment. These patients were younger, had lower erythrocyte sedimentation rates, were less likely to use four or more drugs, and had shorter treatment duration than those who failed to achieve microbiological cure. During a median follow-up of 3.2 (first quartile to third quartile, 1.4-5.4) years after treatment completion, 53 patients died. Microbiological cure was significantly associated with reduced mortality after adjustment for major clinical factors (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.94). The association between microbiological cure and mortality was maintained in a sensitivity analysis that included all patients treated < 12 months. INTERPRETATION: Microbiological cure at completion of treatment is associated with longer survival in patients with MAC-PD.

Ethical Issues Referred to Clinical Ethics Support at a University Hospital in Korea: Three-Year Experience After Enforcement of Life-Sustaining Treatment Decisions Act.

BACKGROUND: Clinical ethics support is a form of preventive ethics aimed at mediating ethics-related conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. METHODS: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultation-related documents. RESULTS: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. CONCLUSION: The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

Prognostic serum biomarkers in non-tuberculous mycobacterial pulmonary disease.

Increased serum C-reactive protein (CRP) levels at the time of diagnosis predicted worse prognosis in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). Approximately one-quarter of the patients with NTM-PD had higher than normal CRP levels, and this elevation led to a higher risk of death.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Impact of Treatment on Long-Term Survival of Patients With Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Whether antimicrobial treatment improves long-term survival in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) is unclear. METHODS: We analyzed survival in patients aged ≥18 years who were treated for MAC-PD at a tertiary referral center in South Korea between 1 January 2009 and 31 December 2020. Treatment exposure was divided into 4 time intervals: <6, ≥6 to <12, ≥12 to <18, and ≥18 months. Time-varying multivariable Cox proportional hazards models were used to calculate the all-cause mortality risk in each time interval. The model was adjusted for major clinical factors related to mortality including age, sex, body mass index, presence of cavities, erythrocyte sedimentation rate, positive acid-fast bacilli (AFB) smear, clarithromycin resistance, and comorbid conditions. RESULTS: A total of 486 patients treated for MAC-PD were included in the analysis. A significant inverse correlation was observed between mortality and duration of treatment (P for trend = .007). Long-term treatment (≥18 months) was significantly associated with reduced mortality (adjusted hazard ratio, 0.32 [95% confidence interval, .15-.71]). In subgroup analyses, patients with cavitary lesions (adjusted hazard ratio, 0.17 [95% confidence interval, .05-.57]) or positive AFB smears (0.13 [.02-.84]) at baseline maintained this significant inverse relationship between treatment duration and mortality. CONCLUSIONS: Long-term antimicrobial treatment should be actively considered in patients with progressive MAC-PD, especially in the presence of cavities or positive AFB smears indicative of high mycobacterial burden.

Mycobacterial cavity on chest computed tomography: clinical implications and deep learning-based automatic detection with quantification.

Background: This study aimed (I) to investigate the clinical implication of computed tomography (CT) cavity volume in tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD), and (II) to develop a three-dimensional (3D) nnU-Net model to automatically detect and quantify cavity volume on CT images. Methods: We retrospectively included conveniently sampled 206 TB and 186 NTM-PD patients in a tertiary referral hospital, who underwent thin-section chest CT scans from 2012 through 2019. TB was microbiologically confirmed, and NTM-PD was diagnosed by 2007 Infectious Diseases Society of America/American Thoracic Society guideline. The reference cavities were semi-automatically segmented on CT images and a 3D nnU-Net model was built with 298 cases (240 cases for training, 20 for tuning, and 38 for internal validation). Receiver operating characteristic curves were used to evaluate the accuracy of the CT cavity volume for two clinically relevant parameters: sputum smear positivity in TB and treatment in NTM-PD. The sensitivity and false-positive rate were calculated to assess the cavity detection of nnU-Net using radiologist-detected cavities as references, and the intraclass correlation coefficient (ICC) between the reference and the U-Net-derived cavity volumes was analyzed. Results: The mean CT cavity volumes in TB and NTM-PD patients were 11.3 and 16.4 cm3, respectively, and were significantly greater in smear-positive TB (P<0.001) and NTM-PD necessitating treatment (P=0.020). The CT cavity volume provided areas under the curve of 0.701 [95% confidence interval (CI): 0.620-0.782] for TB sputum positivity and 0.834 (95% CI: 0.773-0.894) for necessity of NTM-PD treatment. The nnU-Net provided per-patient sensitivity of 100% (19/19) and per-lesion sensitivity of 83.7% (41/49) in the validation dataset, with an average of 0.47 false-positive small cavities per patient (median volume, 0.26 cm3). The mean Dice similarity coefficient between the manually segmented cavities and the U-Net-derived cavities was 78.9. The ICCs between the reference and U-Net-derived volumes were 0.991 (95% CI: 0.983-0.995) and 0.933 (95% CI: 0.897-0.957) on a per-patient and per-lesion basis, respectively. Conclusions: CT cavity volume was associated with sputum positivity in TB and necessity of treatment in NTM-PD. The 3D nnU-Net model could automatically detect and quantify mycobacterial cavities on chest CT, helping assess TB infectivity and initiate NTM-TB treatment.

The Clinical Course and Prognosis of Patients With Nontuberculous Mycobacterial Pulmonary Disease After Solid Organ Transplantation.

BACKGROUND: Due to impaired cell-mediated immunity, solid organ transplantation (SOT) recipients are at increased risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD). However, the clinical course of NTM-PD in SOT patients and the impact of SOT on the prognosis of NTM-PD remain unclear. METHODS: We analyzed patients who developed NTM-PD after receiving SOT between January 2001 and December 2020, at a tertiary referral hospital in South Korea. Baseline characteristics, clinical course, and prognosis were evaluated. Propensity score-matched analysis was performed to assess the impact of SOT on long-term survival in patients with NTM-PD. RESULTS: Among 4,685 SOT recipients over 20 years, 12 patients (median age, 64 years; interquartile range [IQR], 59-67 years; men, 66.7%) developed NTM-PD. Seven (58.3%) and five (41.7%) patients underwent kidney and liver transplantation, respectively, before the diagnosis of NTM-PD. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.7 cases per 100,000 person-years among liver transplant recipients. The median time between transplantation and the diagnosis of NTM-PD was 3.3 (IQR, 1.5-10.8) years. The most common mycobacterial species was Mycobacterium avium (50.0%). Antibiotic treatment was initiated in five (41.7%) patients, and two patients (40.0%) achieved microbiological cure. Two patients died during a median follow-up of 4.2 (IQR, 2.3-8.8) years and NTM-PD was assumed to be the cause of death in one patient. When matched to patients without a history of SOT, patients with a history of SOT did not show worse survival (P value for log-rank test = 0.62). CONCLUSION: The clinical course of NTM-PD in SOT recipients was comparable to that of patients without SOT, and SOT did not increase the risk of all-cause mortality in patients with NTM-PD.

Outcomes of Adjunctive Surgery in Patients With Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. Amidst the poor treatment success of antibiotic therapy, adjunctive surgery is gaining attention; however, discrepancies in reported outcomes exist. RESEARCH QUESTION: What are the treatment outcomes and complications of patients with NTM-PD undergoing adjunctive surgery? STUDY DESIGN AND METHODS: The MEDLINE, Embase, and Cochrane databases were searched for eligible studies before January 2022. Studies reporting the outcomes of adjunctive surgery in adult patients who satisfied the diagnostic criteria for NTM-PD were included. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Data were extracted by two independent observers. Estimates of proportion were pooled using a random-effects model. Sputum mycobacterial culture negative conversion, recurrence, complications, and in-hospital mortality after surgery were primary outcomes that had been set before data collection began. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using funnel plots and the Egger test. RESULTS: Fifteen of the 2,739 screened studies, with 1,071 patients, were assessed. The weighted proportion of postoperative sputum culture negative conversion was 93% (95% CI, 87%-97%), and recurrence was 9% (95% CI, 6%-14%) for a median follow-up of 34 months. The proportion of patients who experienced postoperative complications was 17% (95% CI, 13%-23%), and in-hospital mortality was 0% (95% CI, 0%-2%). Studies that performed multilobar lung resection in > 30% of the study population showed comparable rates of complications with studies that did not. INTERPRETATION: Adjunctive surgery is an effective therapeutic option with acceptable rates of complications for selected patients with NTM-PD. TRIAL REGISTRY: PROSPERO; No.: CRD42022310663; URL: https://www.crd.york.ac.uk/prospero/.

The Rise in Prevalence and Related Costs of Nontuberculous Mycobacterial Diseases in South Korea, 2010-2021.

Between 2010 and 2021, the annual prevalence of nontuberculous mycobacterial (NTM) diseases in South Korea increased from 11.4 to 56.7 cases per 100 000 population. Prevalence in the population aged ≥65 years quadrupled from 41.9 to 163.1 cases per 100 000 population. Accordingly, the overall cost associated with NTM diseases increased.

9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.

BACKGROUND: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis. METHODS: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994. FINDINGS: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group. INTERPRETATION: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis. FUNDING: Korea Disease Control and Prevention Agency, South Korea.

Prospective evaluation of thoracic diseases using a compact flat-panel detector spiral computed tomographic scanner.

Objective: To prospectively evaluate the image quality and diagnostic performance of a compact flat-panel detector (FD) scanner for thoracic diseases compared to a clinical CT scanner. Materials and methods: The institutional review board approved this single-center prospective study, and all participants provided informed consent. From December 2020 to May 2021, 30 patients (mean age, 67.1 ± 8.3 years) underwent two same-day low-dose chest CT scans using clinical state-of-art and compact FDCT scanners. Image quality was assessed visually and quantitatively. Two readers evaluated the diagnostic performance for nodules, parenchymal opacifications, bronchiectasis, linear opacities, and pleural abnormalities in 40 paired CT scans. The other 20 paired CT scans were used to examine the agreement of semi-quantitative CT scoring regarding bronchiectasis, bronchiolitis, nodules, airspace consolidations, and cavities. Results: FDCT images had significantly lower visual image quality than clinical CT images (all p < 0.001). The two CT image sets showed no significant differences in signal-to-noise and contrast-to-noise ratios (56.8 ± 12.5 vs. 57.3 ± 15.2; p = 0.985 and 62.9 ± 11.7 vs. 60.7 ± 16.9; p = 0.615). The pooled sensitivity was comparable for nodules, parenchymal opacifications, linear opacities, and pleural abnormalities (p = 0.065-0.625), whereas the sensitivity was significantly lower in FDCT images than in clinical CT images for micronodules (p = 0.007) and bronchiectasis (p = 0.004). The specificity was mostly 1.0. Semi-quantitative CT scores were similar between the CT image sets (p > 0.05), and intraclass correlation coefficients were around 0.950 or higher, except for bronchiectasis (0.869). Conclusion: Compact FDCT images provided lower image quality but comparable diagnostic performance to clinical CT images for nodules, parenchymal opacifications, linear opacities, and pleural abnormalities.