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Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Filogeografía , Humanos , Mycobacterium kansasii/genética , Mycobacterium kansasii/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Taiwán/epidemiología , Anciano , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/epidemiología , Filogenia , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Riesgo , Secuenciación Completa del GenomaRESUMEN
OBJECTIVES: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing. DISCUSSION: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.
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OBJECTIVES: Predicting progression of nontuberculous mycobacterial lung disease (NTM-LD) remains challenging. This study evaluated whether sputum bacterial microbiome diversity can be the biomarker and provide novel insights into related phenotypes and treatment timing. METHODS: We analyzed 126 sputum microbiomes of 126 patients with newly diagnosed NTM-LD due to Mycobacterium avium complex, M. abscessus complex, and M. kansasii between May 2020 and December 2021. Patients were followed for 2 years to determine their disease progression status. We identified consistently representative genera that differentiated the progressor and nonprogressor by using six methodologies. These genera were used to construct a prediction model using random forest with 5-fold cross validation. RESULTS: Disease progression occurred in 49 (38.6%) patients. Compared with nonprogressors, α-diversity was lower in the progressors. Significant compositional differences existed in the ß-diversity between groups (p=0.001). The prediction model for NTM-LD progression constructed using seven genera (Burkholderia, Pseudomonas, Sphingomonas, Candidatus Saccharibacteria, Phocaeicola, Pelomonas, and Phascolarctobacterium) with significantly differential abundance achieved an area under curve of 0.871. CONCLUSIONS: Identification of the composition of sputum bacterial microbiome facilitates prediction of the course of NTM-LD, and maybe used to develop precision treatment involving modulating the respiratory microbiome composition to ameliorate NTM-LD.
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BACKGROUND: Guideline-based therapy (GBT) for pulmonary Mycobacterium abscessus (Mab) disease achieves sustained sputum culture conversion (SSCC) rates of 30%; this is reflected by poor efficacy of GBT in the hollow fiber system model of Mab (HFS-Mab), which killed â¼1.22 log10 CFU/mL. This study was performed to determine which clinical dose of omadacycline, a tetracycline antibiotic, should be used in combination therapy to treat pulmonary Mab disease for relapse-free cure. METHODS: First, omadacycline intrapulmonary concentration-time profiles of seven daily doses were mimicked in the HFS-Mab model and exposures associated with optimal efficacy were identified. Second, 10,000 subject Monte-Carlo simulations were performed to determine whether oral omadacycline 300 mg/day achieved these optimal exposures. Third, a retrospective clinical study on omadacycline vs. primarily tigecycline-based salvage therapy was conducted to assess rates of SSCC and toxicity. Fourth, a single patient was recruited to validate the findings. RESULTS: Omadacycline efficacy in the HFS-Mab was 2.09 log10 CFU/mL at exposures achieved in >99% of patients on 300 mg/day omadacycline. In the retrospective study of omadacycline 300 mg/day-based combinations vs. comparators, SSCC was achieved in 8/10 vs. 1/9 (P=0.006), symptom improvement in 8/8 vs. 5/9 (P=0.033), toxicity in 0 vs. 9/9 (P<0.001), and therapy discontinuation due to toxicity in 0 vs. 3/9 (P<0.001) cases, respectively. In one prospectively recruited patient, omadacycline 300 mg/day salvage therapy achieved SSCC and symptom-resolution in 3 months. CONCLUSION: Based on the preclinical and clinical data, omadacycline 300 mg/day in combination regimens could be appropriate for testing in Phase III trials in patients with Mab pulmonary disease.
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Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Tetraciclinas/uso terapéutico , Tetraciclinas/farmacología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
Background: Uncontrolled asthma in adults leads to poor clinical outcome, while the clinical heterogeneity of phenotypes interferes the applicable genetic determinants. This study aimed to identify phenotypes and genetic impact on poorly-controlled asthma to optimize individualized treatment strategies. Methods: This propensity score-matched case-control study included 340 and 1020 asthmatics with poorly-controlled asthma and well-controlled asthma, respectively. Data were obtained from the 2008-2015 Taiwan Biobank Database and linked to the National Health Insurance Research Database. All asthmatics were aged ≥30 years, without cancer history, and each completed a questionnaire, physical examination, and genome-wide single nucleotide polymorphisms (SNPs). Multivariate adjusted odds ratios (ORs) for genetic risk scores were calculated using conditional logistic regression, stratified by age and sex. A model integrating obesity- and asthma-associated phenotypes and genotypes was applied for poorly-controlled asthma risk prediction. Results: General obesity with body mass index (BMI) ≥27 kg/m2 (OR:1.49, 95% confidence interval (CI) 1.09-2.03), central obesity with waist-to-height ratio (WHtR) ≥0.5 (OR:1.62, 95% CI 1.22-2.15), and parental history of asthma (OR:1.65, and 1.68; for BMI model and WHtR model, respectively) were significantly associated with poorly-controlled asthma in adults, and the combination effect of both obesity phenotypes was 1.66 (95% CI 1.17-2.35). A total of 16 obesity-associated SNPs and 9 asthma-associated SNPs were converted into genetic scores, and the aforementioned phenotypes were incorporated into the risk prediction model for poorly-controlled asthma, with an area under curve 0.72 in the receiver operating characteristic curve. The potential biological functions of genes are involved in immunity pathways. Conclusion: The prediction model integrating obesity-asthma phenotypes and genotypes for poorly-controlled asthma can facilitate the prediction of high-risk asthma and provide potential targets for novel treatment.
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BACKGROUND: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. METHODS: We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. RESULTS: Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. CONCLUSIONS: The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Tuberculosis Latente , Humanos , Microbioma Gastrointestinal/inmunología , Inmunidad , Tuberculosis Latente/inmunología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunologíaRESUMEN
Invasive aspergillosis (IA) has become the emerging life-threatening disease in recent years. Influenza has been identified as an independent risk factor for IA. Vaccination is the most effective way to prevent influenza, while whether it can reduce IA in high-risk population still uncertain. We aimed to investigate the association between influenza vaccination and the risk of IA in high-risk population. We performed a population-based cohort study of people who qualified for government-funded influenza vaccination and were at high risk for IA at the start of the influenza season each year between 2016 and 2019. We utilized Taiwan's National Health Insurance Research Database to identify the influenza vaccination status and IA diagnosis during the follow-up period. We compared the risk of IA between people with and without vaccination using multivariable logistic regression analysis. Out of total 8,544,451 people who were eligible during the 3 influenza seasons, 3,136,477 (36.7%) were vaccinated. A total of 1179 IA cases with the incidence of 13.8 cases per 100,000 high-risk individuals were identified during the follow-up. Compared to non-vaccinated group, vaccinated individuals had a 21% risk reduction of IA (adjusted odds ratio 0.79, 95% confidence interval 0.70-0.90). Influenza vaccination was associated with a lower risk of IA among males, immunosuppressive conditions, malignancy, diabetes, and those having host factors according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Influenza vaccination is recommended for high-risk population to reduce the risk of IA.
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Aspergilosis , Vacunas contra la Influenza , Gripe Humana , Infecciones Fúngicas Invasoras , Masculino , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Gripe Humana/complicaciones , Estudios de Cohortes , Taiwán/epidemiología , Factores de Riesgo , VacunaciónRESUMEN
AIM: A population pharmacokinetic (PPK) study of the correlation of adverse drug reactions (ADRs) with the 3HP regimen (weekly high-dose rifapentine plus isoniazid for 12 doses) for latent tuberculosis infection (LTBI) remains lacking. The purpose of this study is to determine the association of rifapentine or isoniazid concentration and ADRs. METHODS: This prospective, multicentre, observational study enrolled LTBI contacts receiving 3HP treatment between January 2017 and August 2020. The concentrations of rifapentine, isoniazid and their metabolites (25-desacetyl-rifapentine and acetyl-isoniazid) in plasma samples collected monthly after 3HP treatment were determined. A PPK model was constructed to predict the maximum concentration (Cmax ) and area under the concentration-time curve from 0 to 24 h (AUC). Their association with ADRs was evaluated by applying three multivariate logistic regression models with adjustment for various covariates. RESULTS: A total of 415 LTBI cases were ultimately enrolled; 355 (85.5%) completed the 3HP treatment. Among them, 47 (11.3%) experienced systemic drug reactions and 291 (70.0%) experienced one or more flu-like symptom. The plasma concentration-time profiles of isoniazid, rifapentine and their metabolites were adequately described by the developed models. A higher Cmax of isoniazid was significantly correlated with a higher risk of any ADR (adjusted odds ratio and 95% confidence interval: 3.04 [1.07-8.65]) and any or at least two flu-like symptoms (all severity grades) (2.76 [1.06-7.17]). CONCLUSIONS: Isoniazid may be responsible for ADRs, especially flu-like symptoms, during 3HP treatment.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Tuberculosis Latente , Humanos , Isoniazida/efectos adversos , Antituberculosos/efectos adversos , Estudios Prospectivos , Quimioterapia Combinada , Tuberculosis Latente/epidemiología , Tuberculosis Latente/prevención & control , Tuberculosis Latente/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiologíaRESUMEN
Standard therapy [isoniazid, rifampin, ethambutol], with or without a macrolide, for pulmonary Mycobacterium kansasii lasts more than a year. Therefore, shorter treatment duration regimens are required. We used data from 32 Taiwanese patients treated with standard therapy who were followed using repetitive sampling-based sputum Mkn time-to-positivity in liquid cultures to calculate kill slopes [γ] based on ordinary differential equations and time-to-extinction of each patient's bacterial burden. The γ was 0.18 [95% Confidence Interval (CI): 0.16-0.20] log10 CFU/mL/day on standard therapy. Next, we identified Mkn time-to-extinction in the hollow fiber system model of pulmonary M. kansasii disease [HFS-Mkn] treated with standard therapy, which was a γ of 0.60 [95% CI: 0.45-0.69) log10 CFU/mL/day. The γs and time-to-extinctions between the two datasets formed structure-preserving maps based on category theory: thus, we could map them from one to the other using morphisms. This mapping identified a multistep non-linear transformation-factor for time-to-extinction from HFS-Mkn to patients. Next, a head-to-head study in the HFS-Mkn identified median time-to-extinction for standard therapy of 38.7 [95% CI: 29.1-53.2) days, isoniazid-rifampin-ethambutol-moxifloxacin of 21.7 [95% CI: 19.1-25) days, isoniazid-rifampin-moxifloxacin of 22 [96% CI: 20.1-24.5) days, and rifampin-moxifloxacin-tedizolid of 20.7 [95% CI:18.5-29) days. Our transformation-factor based translation predicted the proportion of patients of 90.7 [88.74-92.35)% achieving cure with standard therapy at 12 months, and 6-months cure rates of 99.8 [95% CI: 99.27-99.95)% for isoniazid-rifampin-ethambutol-moxifloxacin, 92.2 [90.37-93.71)% for isoniazid-rifampin-moxifloxacin, and 99.9 [99.44-99.99)% for rifampin-moxifloxacin-tedizolid. Thus, rifampin-moxifloxacin-tedizolid and isoniazid-rifampin-ethambutol-moxifloxacin are predicted to be short-course chemotherapy regimens for pulmonary M. kansasii disease.
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The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA (n = 128, 84.8%) and those with ≥2 MSAs (n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of "mixed phenotypes". No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs.
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There is limited high-quality evidence to guide the optimal treatment of Mycobacterium kansasii pulmonary disease. We retrospectively collected clinical data from 33 patients with M. kansasii pulmonary disease to determine the time-to-sputum culture conversion (SCC) upon treatment with a standard combination regimen consist of isoniazid-rifampin-ethambutol. Next, MIC experiments with 20 clinical isolates were performed, followed by a dose-response study with the standard laboratory strain using the hollow-fiber system model of M. kansasii infection (HFS-Mkn). The inhibitory sigmoid maximum effect (Emax) model was used to describe the relationship between the bacterial burden and rifampin concentrations. Finally, in silico clinical trial simulations were performed to determine the clinical dose to achieve the optimal rifampin exposure in patients. The SCC rate in patients treated with combination regimen containing rifampin at 10 mg/kg of body weight/day was 73%, the mean time to SSC was 108 days, and the mean duration of therapy was 382 days. The MIC of the M. kansasii laboratory strain was 0.125 mg/L, whereas the MICs of the clinical isolates ranged between 0.5 and 4 mg/L. In the HFS-Mkn model, a maximum kill (Emax) of 7.82 log10 CFU/mL was recorded on study day 21. The effective concentration mediating 80% of the Emax (EC80) was calculated as the ratio of the maximum concentration of drug in serum for the free, unbound fraction (fCmax) to MIC of 34.22. The target attainment probability of the standard 10-mg/kg/day dose fell below 90% even at the MIC of 0.0625 mg/L. Despite the initial kill, there was M. kansasii regrowth with the standard rifampin dose in the HFS-Mkn model. Doses higher than 10 mg/kg/day, in combination with other drugs, need to be evaluated for better treatment outcome.
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Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Antituberculosos/farmacología , Humanos , Enfermedades Pulmonares/microbiología , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Estudios Retrospectivos , Rifampin/uso terapéuticoRESUMEN
BACKGROUND: Systemic drug reaction (SDR) is a major safety concern with weekly rifapentine plus isoniazid for 12 doses (3HP) for latent tuberculosis infection (LTBI). Identifying SDR predictors and at-risk participants before treatment can improve cost-effectiveness of the LTBI program. METHODS: We prospectively recruited 187 cases receiving 3HP (44 SDRs and 143 non-SDRs). A pilot cohort (8 SDRs and 12 non-SDRs) was selected for generating whole-blood transcriptomic data. By incorporating the hierarchical system biology model and therapy-biomarker pathway approach, candidate genes were selected and evaluated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Then, interpretable machine learning models presenting as SHapley Additive exPlanations (SHAP) values were applied for SDR risk prediction. Finally, an independent cohort was used to evaluate the performance of these predictive models. RESULTS: Based on the whole-blood transcriptomic profile of the pilot cohort and the RT-qPCR results of 2 SDR and 3 non-SDR samples in the training cohort, 6 genes were selected. According to SHAP values for model construction and validation, a 3-gene model for SDR risk prediction achieved a sensitivity and specificity of 0.972 and 0.947, respectively, under a universal cutoff value for the joint of the training (28 SDRs and 104 non-SDRs) and testing (8 SDRs and 27 non-SDRs) cohorts. It also worked well across different subgroups. CONCLUSIONS: The prediction model for 3HP-related SDRs serves as a guide for establishing a safe and personalized regimen to foster the implementation of an LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Tuberculosis Latente , Antituberculosos/efectos adversos , Técnicas de Apoyo para la Decisión , Quimioterapia Combinada , Humanos , Isoniazida/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/prevención & control , Rifampin/análogos & derivadosRESUMEN
BACKGROUND AND OBJECTIVE: Obesity and asthma impose a heavy health and economic burden on millions of people around the world. The complex interaction between genetic traits and phenotypes caused the mechanism between obesity and asthma is still vague. This study investigates the relationship among obesity-related polygenic risk score (PRS), obesity phenotypes and the risk of having asthma. METHODS: This is a matched case-control study, with 4 controls (8288 non-asthmatic) for each case (2072 asthmatic). Data were obtained from the 2008-2015 Taiwan Biobank Database and linked to the 2000-2016 National Health Insurance Research Database. All participants were ≥30 years old with no history of cancer and had a complete questionnaire, as well as physical examination, genome-wide single nucleotide polymorphisms and clinical diagnosis data. Environmental exposure, PM2.5, was also considered. Multivariate adjusted ORs and 95% CIs were calculated using conditional logistic regression stratified by age and sex. Mediation analysis was also assessed, using a generalised linear model. RESULTS: We found that the obese phenotype was associated with significantly increased odds of asthma by approximately 26%. Four obesity-related PRS, including body mass index (OR=1.07 (1.01-1.13)), waist circumference (OR=1.10 (1.04-1.17)), central obesity as defined by waist-to-height ratio (OR=1.09 (1.03-1.15)) and general-central obesity (OR=1.06 (1.00-1.12)), were associated with increased odds of asthma. Additional independent risk factors for asthma included lower educational level, family history of asthma, certain chronic diseases and increased PM2.5 exposure. Obesity-related PRS is an indirect risk factor for asthma, the link being fully mediated by the trait of obesity. CONCLUSIONS: Obese phenotypes and obesity-related PRS are independent risk factors for having asthma in adults in the Taiwan Biobank. Overall, genetic risk for obesity increases the risk of asthma by affecting the obese phenotype.
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Asma , Obesidad Abdominal , Humanos , Obesidad Abdominal/complicaciones , Taiwán/epidemiología , Estudios de Casos y Controles , Bancos de Muestras Biológicas , Obesidad/epidemiología , Obesidad/genética , Obesidad/complicaciones , Asma/epidemiología , Asma/genética , Asma/complicaciones , Fenotipo , Material ParticuladoRESUMEN
BACKGROUND: Histologic diagnosis of granuloma is often considered clinically equivalent to a definite diagnosis of pulmonary tuberculosis (TB) in endemic areas. Optimal management of surgically resected granulomatous inflammation in lung with negative mycobacterial culture results, however, remains unclear. METHODS: From 7 medical institutions in northern, middle, and southern Taiwan between January 2010 and December 2018, patients whose surgically resected pulmonary nodule(s) had histological features suggestive of TB but negative microbiological study results and who received no subsequent anti-TB treatment were identified retrospectively. All patients were followed up for 2 years until death or active TB disease was diagnosed. RESULTS: A total of 116 patients were enrolled during the study period. Among them, 61 patients (52.6%) were clinically asymptomatic, and 36 (31.0%) patients were immunocompromised. Solitary pulmonary nodule accounted for 44 (39.6%) of all cases. The lung nodules were removed by wedge resection in 95 (81.9%), lobectomy in 17 (14.7%), and segmentectomy in 4 (3.4%) patients. The most common histological feature was granulomatous inflammation (n=116 [100%]), followed by caseous necrosis (n=39 [33.6%]). During follow-up (218.4 patient-years), none of the patients developed active TB. CONCLUSIONS: In patients with surgically resected culture-negative pulmonary granulomas, the incidence rate of subsequent active TB is low. Watchful monitoring along with regular clinical, radiological, and microbiological follow-up, instead of routine anti-TB treatment, may also be a reasonable option.
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Smoking, sex, air pollution, lifestyle, and diet may act independently or in concert with each other to contribute to the different outcomes of lung cancer (LC). This study aims to explore their associations with the carcinogenesis of LC, which will be useful for formulating further preventive strategies. This retrospective, longitudinal follow-up cohort study was carried out by connecting to the MJ Health Database, Taiwan Cancer Registry database, and Taiwan cause of death database from 2000 to 2015. The studied subjects were persons attending the health check-ups, distributed throughout the main island of Taiwan. Cox proportional hazards regression models were used to investigate the risk factors associated with LC development and mortality after stratifying by smoking status, with a special emphasis on ambient two-year average PM2.5 exposure, using a satellite-based spatiotemporal model at a resolution of 1 km2, and on dietary habit including consumption of fruits and vegetables. After a median follow-up of 12.3 years, 736 people developed LC, and 401 people died of LC-related causes. For never smokers, the risk of developing LC (aHR: 1.32, 95%CI: 1.12-1.56) and dying from LC-related causes (aHR: 1.28, 95%CI: 1.01-1.63) rises significantly with every 10 µg/m3 increment of PM2.5 exposure, but not for ever smokers. Daily consumption of more than two servings of vegetables and fruits is associated with lowering LC risk in ever smokers (aHR: 0.68, 95%CI: 0.47-0.97), and preventing PM2.5 exposure is associated with lowering LC risk for never smokers.