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2.
Sci Rep ; 12(1): 18670, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36333461

ABSTRACT

This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality.


Subject(s)
Community-Acquired Infections , Cross Infection , Healthcare-Associated Pneumonia , Pneumonia, Staphylococcal , Pneumonia , Adult , Humans , Female , Middle Aged , Aged , Staphylococcus aureus , Community-Acquired Infections/diagnosis , Pneumonia, Staphylococcal/epidemiology , Pneumonia, Staphylococcal/drug therapy , Cross Infection/drug therapy , Retrospective Studies , Pneumonia/drug therapy , Healthcare-Associated Pneumonia/drug therapy , Streptococcus pneumoniae , Risk Factors , Anti-Bacterial Agents/therapeutic use
3.
J Am Soc Echocardiogr ; 35(10): 1064-1076, 2022 10.
Article in English | MEDLINE | ID: mdl-35691457

ABSTRACT

BACKGROUND: Stroke of undetermined source, commonly termed cryptogenic stroke (CS), accounts for a significant proportion of ischemic stroke etiology and have high rates of stroke recurrence. The heterogeneous etiology of CS makes decisions regarding treatment for such patients challenging. The aim of this study was to evaluate the diagnostic and prognostic value of left atrial (LA) function in the identification of cardioembolism and prediction of outcomes in patients with CS. METHODS: Consecutive patients admitted to a tertiary institution with ischemic stroke or transient ischemic attack (TIA) who underwent transthoracic echocardiography were recruited, with comprehensive evaluation of LA metrics including LA strain. Ischemic strokes and TIAs were classified as noncardioembolic, cryptogenic, or cardioembolic. A total of 709 patients (mean age, 66.0 ± 15.1 years; 55% men) were recruited. Two hundred ninety-one patients had CS, 189 had noncardioembolic stroke, and 229 had cardioembolic stroke. Patients with CS were followed for 20.0 ± 13.8 months for recurrent ischemic stroke or TIA. RESULTS: Receiver operating characteristic curves showed LA reservoir and contractile strain to be strong discriminators of cardioembolic strokes, and log-rank tests showed both measures to be significantly associated with the distribution of time to recurrent ischemic stroke or TIA in patients with CS. Multivariable hazard models showed LA reservoir and contractile strain to be independent predictors of recurrent ischemic stroke or TIA in patients with CS, in addition to estimated glomerular filtration rate and active smoking. CONCLUSIONS: LA reservoir and contractile strain were strong discriminators of cardioembolic stroke and independently predicted recurrent ischemic stroke or TIA in patients with CS. Use of LA strain may improve risk stratification and decision-making in patients with CS, with particular regard to prolonged ambulatory heart rhythm monitoring and/or empiric anticoagulation.


Subject(s)
Atrial Fibrillation , Embolic Stroke , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Aged , Aged, 80 and over , Anticoagulants , Atrial Function, Left , Embolic Stroke/diagnostic imaging , Embolic Stroke/etiology , Female , Humans , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/diagnostic imaging , Male , Middle Aged , Prognosis , Risk Factors , Stroke/diagnostic imaging , Stroke/etiology
4.
Sci Rep ; 12(1): 6981, 2022 04 28.
Article in English | MEDLINE | ID: mdl-35484186

ABSTRACT

Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, respiratory rate, pulse rate, and blood pressure at the time of pre-HFNC, post-HFNC, pre-NC, and post-NC, were collected and analysed using SPSS (version 25.0, IBM, Armonk, NY, USA). The IOS measurement indicated that HFNC significantly improved R5, R5% predicted, R5-R20, X5-predicted, and Fres compared with NC, whereas no significant difference was observed through the PFT measurement. The beneficial effect of HFNC in improving small airway resistance and peripheral lung reactance compared with that of NC in patients with stable COPD was confirmed through IOS measurement.Trial registration: ClinicalTrials.gov NCT05130112 22/11/2021.


Subject(s)
Cannula , Pulmonary Disease, Chronic Obstructive , Electric Impedance , Forced Expiratory Volume , Humans , Oscillometry/methods , Respiratory Function Tests/methods , Respiratory Rate
5.
Article in English | MEDLINE | ID: mdl-33799568

ABSTRACT

Smart environments and the use of interactive technology has the potential to improve the quality of life for the senior community as well as to support the connections among the senior community and the world outside their community. In addition to the increasing number of studies in the field of aging and technologies, research is needed to understand the practical issues of user focus, adoption, and engagement for older adults to accept interactive technologies in their lives. In this study, we use two commercial technological interventions (uDraw and GrandPad) to understand technology-related perceptions and behaviors of older adults. We present five case studies that emerge from empirical observations of initial engagement with technology through research methods such as focus group discussions, in-depth interviews, observations, and diary studies. The contributions of this study are identification of the key factors that influence the initial engagement with interactive technology for older adults.


Subject(s)
Quality of Life , Technology , Focus Groups
6.
J Neurol Sci ; 418: 117115, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32916515

ABSTRACT

BACKGROUND: Strokes in the young and middle-aged are associated with a disproportionately large economic and social impact in addition to their clinical effects. Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes mellitus and smoking) are key drivers of cardiovascular disease including strokes, however recent temporal trends in the younger stroke population have not been well characterised. We aimed to evaluate recent trends of SMuRFs in a cohort of younger patients with ischaemic stroke. METHODS: Consecutive patients aged <65 years with clinical and/or radiological diagnosis of ischaemic stroke or transient ischaemic attack in a tertiary referral centre (2013-2017) were retrospectively appraised. The demographic and clinical comorbidities of these patients were assessed including their SMuRF profile. The prevalence over time and clinical associations of patients with no SMuRFs were studied and compared to patients with SMuRFs. RESULTS: Of 487 patients (53.49 ± 9.13 yrs., 60% men) analysed, 23% did not have SMuRFs. The proportion of "non-SMuRF" patients increased over time (p < 0.01) and this trend was not influenced by age (p = 0.48) or gender (p = 0.68). The presence of SMuRFs was not associated with in-hospital outcomes, however patients without SMuRFs were significantly less likely to be discharged on blood pressure (p < 0.01) and lipid-lowering therapies (p = 0.03). CONCLUSIONS: The proportion of younger stroke patients without SMuRFs is substantial and has increased over time. Our findings highlight the need for further research to better understand the mechanisms underlying stroke development in this population and whether less risk factor treatment in this population could impact longer term outcomes.


Subject(s)
Brain Ischemia , Cardiovascular Diseases , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Aged , Brain Ischemia/complications , Brain Ischemia/epidemiology , Cardiovascular Diseases/epidemiology , Female , Heart Disease Risk Factors , Humans , Ischemic Attack, Transient/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Stroke/diagnostic imaging , Stroke/epidemiology
7.
J Korean Acad Nurs ; 50(4): 571-582, 2020 Aug.
Article in Korean | MEDLINE | ID: mdl-32895343

ABSTRACT

PURPOSE: This study aimed to determine the effects of a 12-week metabolic syndrome BeHaS (Be Happy and Strong) program in elderly people with metabolic syndrome living alone, based on a community-based participatory research (CBPR). METHODS: A nonequivalent control group pre-posttest design was used, and the participants were 43 elderly people living alone (experimental group 24, control group 19). The experimental group received a one-hour program per week and two individual health consultations during 12 weeks. The control group received two sessions about the metabolic syndrome and two individual health consultations. The effects of health behavior, blood pressure, blood sugar levels, abdominal circumference, triglycerides, and self-esteem were evaluated. The data were analyzed using the independent t-test and Mann-Whitney U test. RESULTS: The health behavior with respect to the metabolic syndrome in the experimental group increased significantly (t = - 3.19, p = .002). Both diastolic blood pressure and abdominal circumference decreased in the experimental group (t = 2.00, p = .028 and t = 3.91, p < .001). No significant differences were observed between the groups in systolic blood pressure, fasting blood sugar levels, triglycerides, and self-esteem. CONCLUSION: The 12-week metabolic syndrome BeHaS program using community resources improves the health of elderly people with metabolic syndrome living alone. Based on these findings, further studies on the effectiveness of the metabolic syndrome BeHaS program and the experiences of those who participated in the CBPR are warranted.


Subject(s)
Health Behavior , Metabolic Syndrome/psychology , Program Evaluation , Self Concept , Aged , Blood Glucose/analysis , Blood Pressure , Community-Based Participatory Research , Female , Health Promotion , Humans , Male , Metabolic Syndrome/pathology , Triglycerides/blood , Waist Circumference
8.
Int J Cardiol Heart Vasc ; 26: 100454, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31909178

ABSTRACT

BACKGROUND: Stroke is one of the leading causes of morbidity and mortality with a significant percentage classified as cryptogenic. Left atrial (LA) remodelling, a substrate for atrial fibrillation (AF) and stroke development, may play a role in identification of the aetiology of cryptogenic stroke. We aimed to examine LA function to gain mechanistic insights into the pathophysiology of cryptogenic stroke in young patients otherwise at low risk for cardiovascular disease. METHODS: Patients aged <60 years without traditional cardiovascular risk factors and who were diagnosed with ischaemic cryptogenic stroke or TIA were evaluated and compared to healthy controls and patients with paroxysmal AF with a CHA2DS2-VA score of 0. Conventional and novel left ventricular (LV) and LA echocardiographic parameters between the three groups were assessed. RESULTS: Each group consisted of thirty patients. There were no significant differences in LV parameters (LVEF, LV endoGLS) between groups. LA strain in stroke patients was significantly lower compared to the controls (median 33%; interquartile range (IQ) [32/39] vs 31 [27/34]; p = 0.008). LA strain was significantly lower in AF patients compared to stroke patients (median 21% [19/22] vs 31% [27/34]; p < 0.0001). CONCLUSION: A stepwise reduction in measures of LA function was appreciated between controls, young stroke and paroxysmal AF groups. This may indicate dynamic LA remodelling occurring in the young stroke population and suggest a shared causal mechanism for stroke development in this group. LA strain may further refine the risk for cardioembolic stroke.

9.
J Formos Med Assoc ; 119(1 Pt 2): 367-376, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31262613

ABSTRACT

BACKGROUND/PURPOSE: Little remains known regarding whether newer FQ with less anti-mycobacterial activity (gemifloxacin) would reduce treatment delay. METHODS: We identified one hospital-based cohort (HBC) and one population-based cohort (PBC) including patients receiving amoxicillin/clavulanate acid (Beta-lactam), gemifloxacin (Gemi), and fluoroquinolones other than gemifloxacin (Non-Gemi FQ) prior to TB treatment. RESULTS: A total of 201 patients in the HBC and 3544 patients in the PBC were recruited. After 1:1 propensity score matching, TB treatment delay was statistically insignificant between Beta-lactam, Gemi group, and Non-Gemi FQ group in HBC (Beta-lactam vs Gemi: 22.3 ± 21.4 d vs 28.6 ± 27.9 d, p = 0.292; Beta-lactam vs Non-Gemi FQ: 33.3 ± 26.5 d vs 50.3 ± 47.3 d, p = 0.135) and PBC (Beta-lactam vs Gemi: 26.4 ± 29.1 vs 25.0 ± 28.1, p = 0.638; Beta-lactam vs Non-Gemi FQ: 29.4 ± 36.0 d vs 32.7 ± 35.0 d, p = 0.124, Non-Gemi FQ vs Gemi: 28.4 ± 33.0 d vs 25.0 ± 28.1 d, p = 0.29). CONCLUSION: While limited by relatively low case number, our study showed that use of gemifloxacin neither results in nor reduces delay in TB treatment. The issue of FQ use on TB treatment delay was also not observed in our study. Early survey and maintaining high clinical alertness remains the key to reducing TB treatment delay.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Fluoroquinolones/therapeutic use , Time-to-Treatment/statistics & numerical data , Tuberculosis/drug therapy , Adult , Aged , Aged, 80 and over , Antitubercular Agents/therapeutic use , Cohort Studies , Databases, Factual , Female , Gemifloxacin/therapeutic use , Hospitals/statistics & numerical data , Humans , Male , Middle Aged , Propensity Score , Taiwan
10.
J Clin Med ; 8(8)2019 Aug 13.
Article in English | MEDLINE | ID: mdl-31412578

ABSTRACT

BACKGROUND: Hepatotoxicity is the most severe adverse effect of anti-tuberculosis therapy. Isoniazid's metabolite hydrazine is a mitochondrial complex II inhibitor. We hypothesized that mitochondrial DNA variants are risk factors for drug-induced liver injury (DILI) due to isoniazid, rifampicin or pyrazinamide. METHODS: We obtained peripheral blood from tuberculosis (TB) patients before anti-TB therapy. A total of 38 patients developed DILI due to anti-TB drugs. We selected 38 patients with TB but without DILI as controls. Next-generation sequencing detected point mutations in the mitochondrial DNA genome. DILI was defined as ALT ≥5 times the upper limit of normal (ULN), or ALT ≥3 times the ULN with total bilirubin ≥2 times the ULN. RESULTS: In 38 patients with DILI, the causative drug was isoniazid in eight, rifampicin in 14 and pyrazinamide in 16. Patients with isoniazid-induced liver injury had more variants in complex I's NADH subunit 5 and 1 genes, more nonsynonymous mutations in NADH subunit 5, and a higher ratio of nonsynonymous to total substitutions. Patients with rifampicin- or pyrazinamide-induced liver injury had no association with mitochondrial DNA variants. CONCLUSIONS: Variants in complex I's subunit 1 and 5 genes might affect respiratory chain function and predispose isoniazid-induced liver injury when exposed to hydrazine, a metabolite of isoniazid and a complex II inhibitor.

11.
BMC Infect Dis ; 18(1): 64, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29390977

ABSTRACT

BACKGROUND: Tuberculosis (TB) remains one of the major infectious diseases worldwide. Adverse reactions are common during TB treatment. Few reports, however, are available on treatment-related acute biliary events (ABEs), such as cholelithiasis, biliary obstruction, acute cholecystitis, and cholangitis. METHODS: We first report four pulmonary TB patients who developed ABEs during anti-TB treatment. Abdominal sonography revealed multiple gall stones with dilated intrahepatic ducts in three patients and cholecystitis in one patient. To investigate the incidence of and risk factors for ABEs during anti-TB treatment, we subsequently conducted a nationwide cohort study using the National Health Insurance Research Database of Taiwan. RESULTS: A total of 159,566 pulmonary TB patients were identified from the database between 1996 and 2010, and among them, 195 (0.12%) developed ABEs within 180 days after beginning anti-TB treatment. Logistic regression analysis revealed that the risk factors associated with ABEs are older age (relative risk [RR]: 1.32 [1.21-1.44] per 10-year increment) and diabetes mellitus (RR: 1.59 [1.19-2.13]). CONCLUSIONS: Although infrequently encountered, ABEs should be considered among patients with TB who experience abdominal discomfort with hyperbilirubinemia, especially patients who have older age or diabetes.


Subject(s)
Antitubercular Agents/adverse effects , Biliary Tract Diseases/etiology , Adult , Aged, 80 and over , Antitubercular Agents/therapeutic use , Bile Duct Diseases/epidemiology , Bile Duct Diseases/etiology , Biliary Tract Diseases/epidemiology , Cholangitis/epidemiology , Cholangitis/etiology , Cholelithiasis/epidemiology , Cholelithiasis/etiology , Cohort Studies , Databases, Factual , Hospitals , Humans , Incidence , Logistic Models , Male , Middle Aged , Risk Factors , Taiwan/epidemiology , Tuberculosis/drug therapy
12.
Sci Rep ; 7(1): 16300, 2017 11 24.
Article in English | MEDLINE | ID: mdl-29176633

ABSTRACT

Multicenter, longitudinal studies on nontuberculous mycobacteria (NTM) pulmonary infection (PI) are lacking. This study provides a 5-year epidemiological overview of NTM-PI in Taiwan and investigated its predictors. The clinical relevance of each respiratory NTM isolate in six hospitals between 2008 and 2014 was determined according to current guidelines. Recurrent episodes were judged by serial bacteriological results. New episodes of NTM-PI and pulmonary colonization (PC) occurring since 2010 were analyzed. Logistic regression analysis was performed to identify the predictors of NTM-PI. Between 2010 and 2014, the incidence rate of NTM-PI was 46.0 episodes per 100,000 hospital-based patient-years. Mycobacterium avium intracellulare complex (MAC) was predominant in Northern Taiwan, whereas MAC and M. abscessus were copredominant in Southern Taiwan. Multiple episodes occurred in 9.5% of NTM-PI patients. No female predominance was observed, except for MAC-PI. Previous pulmonary tuberculosis and chronic obstructive pulmonary disease (COPD) were the most common pulmonary comorbidities and independent risk factors for NTM-PI. Other risk factors included M. kansasii, M. abscessus, and southern Taiwan. Geographical variation of NTM-PI exists in Taiwan. Clinicians should keep a high suspicion on NTM-PI in the risk population. In endemic area of tuberculosis and COPD, there may be no female predominance in NTM-PI.


Subject(s)
Mycobacterium Infections, Nontuberculous/embryology , Nontuberculous Mycobacteria/pathogenicity , Adult , Aged , Female , Humans , Logistic Models , Lung/microbiology , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/metabolism , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium avium-intracellulare Infection/epidemiology , Mycobacterium avium-intracellulare Infection/metabolism , Mycobacterium avium-intracellulare Infection/microbiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/microbiology , Retrospective Studies , Risk Factors , Taiwan , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/metabolism , Tuberculosis, Pulmonary/microbiology
14.
Respir Res ; 18(1): 128, 2017 06 26.
Article in English | MEDLINE | ID: mdl-28651576

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the most common infectious diseases worldwide. During active tuberculosis, T helper (Th) 17 cells are decreased, however the association with inhibitory immune regulation is unclear. METHODS: We enrolled 27 patients with TB and 20 age- and sex-matched controls and studies their lymphocyte status. Peripheral blood lymphocytes were isolated and programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) were measured on Th17 cells by using flow cytometry after the cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 6 h. In addition, Th2 and regulatory T cells were measured and analyzed. RESULTS: The TB group had lower levels of Th17 cells but higher levels of Th2 and Treg cells than the controls. In Th17 cells, the percentage of PD-L1 was higher in the TB group than that in the controls. In Th2 and Treg cells, the percentage of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was lower in the TB group and PD-1 was higher in Treg cells in the TB group. In the patients with extra-pulmonary TB, levels of Th1, Th2 and T17 cells were lower than those with pulmonary TB. The percentage of PD-1 on Th1 lymphocytes positively correlated with radiographic score. CONCLUSIONS: Lower level of Th17 in TB patients may be associated with increased percentage of PD-L1 and increasing levels of Th2 and Treg cells which influenced by CTLA-4.


Subject(s)
B7-H1 Antigen/blood , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolism , Th2 Cells/metabolism , Tuberculosis/blood , Adult , Aged , B7-H1 Antigen/immunology , Female , Humans , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Prospective Studies , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Tuberculosis/diagnosis , Tuberculosis/immunology
15.
BMC Infect Dis ; 17(1): 449, 2017 06 24.
Article in English | MEDLINE | ID: mdl-28646854

ABSTRACT

BACKGROUND AND OBJECTIVE: Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group. METHODS: Adult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment. RESULTS: Among the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65-79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12-128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8-122) days in patients aged 65-79 years, and 78.9%, 6.5% and 21 (1-84) days in patients aged <65 years, respectively. The elder patients were more likely to receive second-line anti-tuberculosis agents. The treatment completion rate decreased with older age, female sex, comorbidities, low income, requiring second-line anti-tuberculosis agents, severity of pulmonary tuberculosis and longer treatment delay. Older age, female sex, comorbidities, low income, and not undergoing rapid molecular diagnostic tests were independently associated with longer treatment delays. CONCLUSIONS: Pulmonary tuberculosis in advanced age has a longer treatment delay and a higher mortality rate. Applying rapid molecular diagnostic tools may reduce treatment delay and should be integrated into the diagnostic algorithm for pulmonary tuberculosis, particularly in elderly patients.


Subject(s)
Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/mortality , Age Factors , Aged , Aged, 80 and over , Antitubercular Agents/therapeutic use , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Taiwan/epidemiology , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis
16.
Sci Rep ; 7: 42004, 2017 02 07.
Article in English | MEDLINE | ID: mdl-28169347

ABSTRACT

Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activation. Partially blocking PD-1 and the PD ligand with antagonizing antibodies in the stimulation assay significantly increased the cytokine production of IFN-γ and decreased the apoptosis on T lymphocytes. In conclusion, the patients with MAC-LD have attenuated lymphocyte immunity, which might be associated with increasing activation of PD-1 and PD-1 ligand. Regulating such activation might improve the lymphocytic secretion of IFN-γ and reduce apoptosis.


Subject(s)
Apoptosis , B7-H1 Antigen/metabolism , Leukocytes, Mononuclear/immunology , Lung Diseases/immunology , Lymphocytes/immunology , Mycobacterium avium Complex/immunology , Mycobacterium avium-intracellulare Infection/complications , Programmed Cell Death 1 Receptor/metabolism , B7-H1 Antigen/immunology , Case-Control Studies , Cytokines/metabolism , Female , Humans , Lung Diseases/microbiology , Lung Diseases/pathology , Lymphocyte Activation , Macrophage Activation , Male , Middle Aged , Programmed Cell Death 1 Receptor/immunology , Prospective Studies
17.
Am J Respir Crit Care Med ; 195(3): 369-382, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27858493

ABSTRACT

RATIONALE: How host genetic factors affect Mycobacterium tuberculosis (Mtb) infection outcomes remains largely unknown. SP110b, an IFN-induced nuclear protein, is the nearest human homologue to the mouse Ipr1 protein that has been shown to control host innate immunity to Mtb infection. However, the function(s) of SP110b remains unclear. OBJECTIVES: To elucidate the role of SP110b in controlling host immunity and susceptibility to tuberculosis (TB), as well as to identify the fundamental immunological and molecular mechanisms affected by SP110b. METHODS: Using cell-based approaches and mouse models of Mtb infection, we characterized the function(s) of SP110b/Ipr1. We also performed genetic characterization of patients with TB to investigate the role of SP110 in controlling host susceptibility to TB. MEASUREMENTS AND MAIN RESULTS: SP110b modulates nuclear factor-κB (NF-κB) activity, resulting in downregulation of tumor necrosis factor-α (TNF-α) production and concomitant upregulation of NF-κB-induced antiapoptotic gene expression, thereby suppressing IFN-γ-mediated monocyte and/or macrophage cell death. After Mtb infection, TNF-α is also downregulated in Ipr1-expressing mice that have alleviated cell death, less severe necrotic lung lesions, more efficient Mtb growth control in the lungs, and longer survival. Moreover, genetic studies in patients suggest that SP110 plays a key role in modulating TB susceptibility in concert with NFκB1 and TNFα genes. CONCLUSIONS: These results indicate that SP110b plays a crucial role in shaping the inflammatory milieu that supports host protection during infection by fine-tuning NF-κB activity, suggesting that SP110b may serve as a potential target for host-directed therapy aimed at manipulating host immunity against TB.


Subject(s)
Antigens, Nuclear , Autoantigens , Epistasis, Genetic/immunology , Genetic Predisposition to Disease , Immunity, Innate/genetics , Minor Histocompatibility Antigens , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/immunology , Nuclear Proteins , Tuberculosis/genetics , Tuberculosis/immunology , Animals , Antigens, Nuclear/genetics , Antigens, Nuclear/immunology , Apoptosis/genetics , Apoptosis/immunology , Autoantigens/genetics , Autoantigens/immunology , Disease Models, Animal , Gene Expression Regulation/immunology , Humans , Mice , Microarray Analysis , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/immunology , NF-kappa B/genetics , NF-kappa B/immunology , Nuclear Proteins/genetics , Nuclear Proteins/immunology , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
18.
Sci Rep ; 6: 37266, 2016 11 23.
Article in English | MEDLINE | ID: mdl-27876856

ABSTRACT

Nontuberculous mycobacteria (NTM)-lung disease (LD) is an increasing health problem worldwide. The diagnosis of this disease remains difficult, however the application of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) has not yet been studied. We screened patients with Mycobacterium avium complex or M. abscessus isolated from sputum, and enrolled 32 patients with NTM-LD and 93 with NTM pulmonary colonization. The NTM-LD group had a lower body mass index, higher proportion of bronchiectasis, more respiratory symptoms and pulmonary lesions, and higher titers of sputum acid-fast stain than the NTM pulmonary colonization group. The plasma level of PlGF was lower in the NTM-LD group than in the NTM colonization group, whereas the level of VEGF was higher in the NTM-LD group. In multivariable logistic regression analysis excluding NTM cultures, the predictive model for NTM-LD included sputum AFS titer, a nodular-bronchiectasis radiographic pattern, plasma VEGF/PlGF ratio, and chest radiographic score (VEGF/P1GF ratio became not significant as a factor in multivariable generalized linear model). The four-factor predictive index had good positive likelihood ratio and negative likelihood ratio for predicting NTM-LD in the patients with NTM in their sputum.


Subject(s)
Lung Diseases/blood , Lung Diseases/microbiology , Mycobacterium Infections, Nontuberculous/blood , Mycobacterium abscessus , Mycobacterium avium , Placenta Growth Factor/blood , Vascular Endothelial Growth Factor A/blood , Aged , Bronchiectasis/blood , Bronchiectasis/diagnostic imaging , Bronchiectasis/microbiology , Humans , Lung Diseases/diagnostic imaging , Middle Aged , Mycobacterium Infections, Nontuberculous/diagnostic imaging , Taiwan
19.
Sci Rep ; 6: 34577, 2016 10 05.
Article in English | MEDLINE | ID: mdl-27703202

ABSTRACT

The interferon-gamma release assay (IGRA) is useful for diagnosing latent tuberculosis infection (LTBI), however the rate of negative conversion is high, especially in dialysis patients. Few studies have focused on predicting persistently positive patients who are at high risk of tuberculosis reactivation. We screened dialysis patients, and used QuantiFERON-TB Gold In-tube (QFT-GIT) to identify LTBI. Of the 157 participants who had initially positive QFT-GIT, 82 had persistently positivity and 75 had negative conversion. The persistently positive group were younger, more were current smokers, and had higher plasma level of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and QFT-GIT responses than the negative conversion group. Multivariate logistic regression for persistent positivity revealed that high plasma sTREM-1 and QFT-GIT response, young age and TB contact history were independent factors. Currently smoking had borderline significance. The area under the receiver operating characteristic curve using the multi-factor model was 0.878, higher than 0.821 by QFT-GIT response of 0.95 IU/ml. In conclusion, dialysis patients with persistent LTBI status may be associated with a young age, high plasma sTREM-1, strong QFT-GIT response, currently smoking, and TB contact history. If resources are limited, these five predictors can be used to prioritize QFT-GIT-positive dialysis patients for LTBI treatment.


Subject(s)
Inflammation Mediators/blood , Interferon-gamma/blood , Latent Tuberculosis/blood , Renal Dialysis , Age Factors , Aged , Biomarkers/blood , Female , Humans , Latent Tuberculosis/therapy , Male , Middle Aged , Triggering Receptor Expressed on Myeloid Cells-1/blood
20.
Medicine (Baltimore) ; 95(22): e3813, 2016 May.
Article in English | MEDLINE | ID: mdl-27258523

ABSTRACT

Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6-month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT-GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs.


Subject(s)
Interferon-gamma Release Tests/methods , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Renal Dialysis/statistics & numerical data , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Predictive Value of Tests , Prevalence , Taiwan/epidemiology , Tuberculosis/epidemiology , Tuberculosis/physiopathology
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