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1.
Yonsei Med J ; 62(3): 224-230, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33635012

RESUMO

PURPOSE: Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD. MATERIALS AND METHODS: WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCD-candidate genes, and 990 ciliome genes were analyzed. RESULTS: Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114, DNAH5, HYDIN, and NME5. In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants. CONCLUSION: At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.

2.
Chest ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33621600

RESUMO

BACKGROUND: Mycobacterium abscessus-pulmonary disease (MABS-PD) is challenging to treat due to its resistance to antibiotics. RESEARCH QUESTION: What are the outcomes of treatment-naïve MABS-PD patients treated with inhaled amikacin-containing multidrug regimens? STUDY DESIGN AND METHODS: We identified 82 treatment-naïve MABS-PD patients from a prospective observational cohort who were treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received intravenous amikacin, imipenem (or cefoxitin) and oral azithromycin. Oral clofazimine was added in cases of (i) M. abscessus subspecies abscessus (here M. abscessus) or (ii) M. abscessus subspecies massiliense (here M. massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from injection to inhalation form. RESULTS: Of 82 patients, 46 (56%) had M. massiliense-PD and 36 (44%) had M. abscessus-PD. Among 59 (72%) patients with nodular bronchiectatic disease, 23 (23/59) had a concurrent cavitary lesion. The remaining 23 (28%) patients had fibrocavitary disease. At 12 months after treatment initiation, cure was achieved in 53 (65%) patients; 42 (42/46, 91%) patients with M. massiliense-PD and 11 (11/36, 31%) patients with M. abscessus-PD (p<0.001). Symptomatic and radiological improvements were observed in 72 (88%) and 64 (78%) patients, respectively, with significantly greater improvement in M. massiliense-PD (96% vs 78% in symptom, p=0.047; 93% vs. 61% in computed tomography, p=0.002). INTERPRETATION: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M. massiliense-PD. However, more effective treatments are needed for M. abscessus-PD.

3.
Eur Respir J ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542050

RESUMO

RATIONALE: Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear. OBJECTIVES: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen. METHODS: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping. RESULTS: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64E-13, odds ratio=0.54), which is in an intronic region of the calcineurin like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. This SNP was also significantly associated with the disease in patients of Korean (p=2.18E-12, odds ratio=0.54) and European (p=5.12E-03, odds ratio=0.63) ancestry. CONCLUSIONS: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.

4.
Exp Mol Med ; 53(1): 136-149, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33473145

RESUMO

Infection with rapidly growing nontuberculous mycobacteria is emerging as a global health issue; however, key host factors remain elusive. Here, we investigated the characteristic immune profiles of peripheral blood mononuclear cells (PBMCs) from patients infected with Mycobacteroides abscessus subsp. abscessus (Mabc) and M. abscessus subsp. massiliense (Mmass). Using an integrated analysis of global mRNA and microRNA expression profiles, we found that several inflammatory cytokines/chemokines [interleukin (IL)-1ß, IL-6, C-X-C motif chemokine ligand 2, and C-C motif chemokine ligand 2] and miR-144-3p were significantly upregulated in PBMCs from patients compared with those from healthy controls (HCs). Notably, there was a strong correlation between the expression levels of miR-144-3p and proinflammatory cytokines/chemokines. Similarly, upregulated expression of miR-144-3p and proinflammatory cytokines/chemokines was found in macrophages and lungs from mice after infection with Mabc and Mmass. We showed that the expression of negative regulators of inflammation (SARM1 and TNIP3) was significantly downregulated in PBMCs from the patients, although they were not putative targets of miR-144-3p. Furthermore, overexpression of miR-144-3p led to a marked increase in proinflammatory cytokines/chemokines and promoted bacterial growth in macrophages. Together, our results highlight the importance of miR-144-3p linking to pathological inflammation during M. abscessus infection.

5.
Clin Infect Dis ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926135

RESUMO

BACKGROUND: Population-based studies on the mortality burden of nontuberculous mycobacteria (NTM) infection are lacking. We compared the long-term mortality of NTM-infected patients with tuberculosis (TB)-patients and the general-population, and investigated mortality-associated factors. METHODS: We analyzed nationwide-data from the Korean National Health Insurance and Korea-Statistical Office between 2002 and 2017. NTM infection was identified using the International Classification of Disease, Tenth Revision code, with one-to-one matching to TB patients and general population controls. RESULTS: A total of 530,401 individuals were analyzed, including 183,267 with NTM infections; 166,666 with TB; and 180,468 controls. The overall 6-, 10-, and 14-year cumulative survival probabilities in the NTM group were 86.3%, 80.8%, and 77.1%, respectively, which were significantly lower than those of the TB or control groups (log-rank p<0.0001). In cases of NTM and TB coinfection, the overall 6-, 10-, and 14-year cumulative survival probabilities were 75.1%, 65.4%, and 57.0%, respectively. Multivariable analysis indicated that old age, male gender, province, and various respiratory or non-respiratory comorbidities were significantly associated with mortality of NTM infection. The use of a macrolide (more than one year) negatively correlated with mortality of NTM infection (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.53-0.71), regardless of azithromycin (aHR 0.60, 95% CI 0.43-0.85) or clarithromycin use (aHR 0.63, 95% CI 0.53-0.75). CONCLUSIONS: NTM-infected patients had poor prognosis when compared to TB patients or the general population, especially for NTM and TB coinfection. NTM mortality was associated with certain demographic characteristics, but long-term use of macrolides may provide survival benefits.

6.
Clin Infect Dis ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910814

RESUMO

Adverse events are frequent in NTM pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus and GI upset. These opinions can provide assistance in individual patient management decisions.

7.
J Clin Med ; 9(9)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937940

RESUMO

Limited data are available regarding optimal treatment for refractory Mycobacterium avium complex-pulmonary disease (MAC-PD). We evaluated outcomes of inhaled amikacin (AMK) with clofazimine (CFZ) regimens as an add-on salvage therapy for refractory MAC-PD. We retrospectively analyzed 52 patients with refractory MAC-PD, characterized by persistently positive sputum cultures despite >6 months of treatment. Thirty-five (67%) patients had M. intracellulare-PD, and 17 (33%) patients had M. avium-PD. Twenty-seven (52%) patients received the salvage therapy for ≥12 months, whereas 25 (48%) patients were treated for <12 months due to adverse effects or other reasons. Seventeen (33%) patients had culture conversion: 10 (10/27) in the ≥12-month treatment group and seven (7/25) in the <12-month treatment group (p = 0.488). Microbiological cure, defined as maintenance of culture negativity, was achieved in 12 (23%) patients; six (6/12) with accompanying symptomatic improvement were considered to have reached cure. Clinical cure, defined as symptomatic improvement with <3 consecutive negative cultures, was achieved in three (6%) patients. Overall, 15 (29%) patients achieved favorable outcomes, including microbiological cure, cure, and clinical cure. Inhaled AMK with CFZ may provide favorable outcomes in some patients with refractory MAC-PD. However, given the adverse effects, more effective strategies are needed to maintain these therapeutic regimens.

8.
Yonsei Med J ; 61(8): 670-678, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734730

RESUMO

PURPOSE: The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. MATERIALS AND METHODS: Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. RESULTS: Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. CONCLUSION: Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Fungos/crescimento & desenvolvimento , Agulhas , Idoso , Feminino , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico
9.
Artigo em Inglês | MEDLINE | ID: mdl-32721164

RESUMO

Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed. Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease. Methods: We included patients age ≥20 years, newly diagnosed with nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort. Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m2 (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval: 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval: 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5. Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense.

10.
J Clin Med ; 9(7)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664449

RESUMO

Aspergillus nodules represent a subtype of chronic pulmonary aspergillosis, but details on their characteristics and outcomes are limited. We evaluated 80 patients with pathologically confirmed Aspergillus nodules between January 2009 and December 2016. The median age of the patients was 59 years, and 46 (58%) were women. Seventy-three (91%) patients were surgically diagnosed with Aspergillus nodules and the remaining seven (9%) patients were diagnosed by percutaneous transthoracic needle biopsy. The median long-axis diameter of nodules was 22 mm, and nodules had an internal cavity in 49 (61%) patients. Spiculation and calcification were observed in 20% and 39% of patients, respectively. Ninety percent (18/20) of nodules showed uptake on positron emission tomography. Serum Aspergillus precipitin IgG antibody was positive in 42% (10/24) of tested patients. Seventy-three (91%) patients underwent surgery without (n = 58) or with (n = 15) adjuvant antifungal therapy, and the remaining seven (9%) patients received antifungal therapy alone (n = 5) or no treatment (n = 2). Three patients experienced postoperative pulmonary complications: pneumothorax, hemoptysis, and acute lung injury (n = 1 each). There was no recurrence during the median follow-up period of 36.8 months. In conclusion, surgery could be a treatment strategy worth considering for most Aspergillus nodules. However, given that our study population was heterogeneous, further well-designed studies are need.

11.
J Clin Med ; 9(5)2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32375214

RESUMO

Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection.

12.
Tuberc Respir Dis (Seoul) ; 83(2): 141-146, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32185919

RESUMO

BACKGROUND: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA). METHODS: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected. CONCLUSION: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.

13.
Sci Rep ; 10(1): 3178, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081976

RESUMO

Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.


Assuntos
Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Pneumopatias/genética , MicroRNAs/genética , Infecções por Mycobacterium não Tuberculosas/genética , Área Sob a Curva , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Pneumopatias/sangue , Pneumopatias/complicações , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/sangue , Infecções por Mycobacterium não Tuberculosas/complicações , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
PLoS One ; 15(2): e0229299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069313

RESUMO

INTRODUCTION: The maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM. MATERIALS AND METHODS: Medical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used. RESULTS: Among the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype. CONCLUSIONS: SUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico por imagem , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxa de Sobrevida
15.
Respir Med ; 161: 105853, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056727

RESUMO

BACKGROUND: Limited data exist on the development of tuberculosis (TB) in cancer patients receiving immune checkpoint inhibitors (ICIs). METHOD: s: We evaluated the development of TB in 1144 solid-cancer patients who started ICIs (pembrolizumab, nivolumab, or atezolizumab) between July 2014 and December 2018. RESULTS: A total of 1144 cancer patients were treated with ICIs. The median age of the patients at the start of ICI treatment was 62 years (interquartile range [IQR]; 53-69 years). Lung cancer (n = 796, 69.6%) was the most common cancer followed by melanoma (n = 115, 10.1%), and lymphoma (n = 85, 7.4%). Pembrolizumab (n = 612, 53.5%) was the most common treatment, followed by nivolumab (n = 474, 41.4%) and atezolizumab (n = 58, 5.1%). The median treatment duration with ICIs was 42 days (IQR; 18-154 days), and the median follow-up duration after initiating ICIs was 187 days (IQR; 70-342 days). Overall, three patients developed TB, two of whom received nivolumab and one who received pembrolizumab. CONCLUSIONS: Our data showed that TB can develop in cancer patients receiving ICIs. However, due to the small number of study population, it is insufficient to draw accurate conclusions about the role of ICIs in the development of TB. Moreover, it is unclear whether the incidence of TB would be comparable with the incidence of TB in elderly cancer patients. Further studies are needed to evaluate whether diagnosis and treatment of latent TB infections before starting ICIs could be helpful in preventing the development of TB in these patients.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/complicações , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Tuberculose Pulmonar/etiologia , Idoso , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Tuberculose Pulmonar/epidemiologia
16.
Tuberc Respir Dis (Seoul) ; 83(1): 20-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31905429

RESUMO

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only first-line drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

17.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31619468

RESUMO

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.

18.
Ann Lab Med ; 40(2): 169-173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31650734

RESUMO

The GENEDIA MTB/NTM Detection Kit (GENEDIA MTB/NTM; Green Cross Medical Science Corp., Chungbuk, Korea) is a multiplex real-time PCR assay used for differential identification of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM). While the importance of differential identification of MTB/NTM is recognized, there is limited data on the performance of GENEDIA MTB/NTM assay to date. A total of 687 consecutive sputum specimens were cultured and analyzed with the GENEDIA MTB/NTM and GENEDIA MTB assays. Nineteen specimens (2.8%) were MTBC-positive, and 69 (10.0%) were NTM-positive based on mycobacterial culture. All specimens showed concordant results for MTBC using both assays, with a kappa value of 1.00, overall sensitivity of 63.2% (12/19), and specificity of 100% (668/668). The overall NTM sensitivity and specificity were 23.2% (16/69) and 99.7% (616/618) for GENEDIA MTB/NTM. The association between NTM-positivity using GENEDIA MTB/NTM and the diagnosis of NTM pulmonary disease was not statistically significant. In conclusion, the two real-time PCR assays showed similar diagnostic performance for MTBC detection. However, the sensitivity for NTM detection was lower than that for MTBC detection.


Assuntos
Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium tuberculosis/genética , Micobactérias não Tuberculosas/genética , Escarro/microbiologia , Tuberculose/diagnóstico , DNA Bacteriano/análise , Humanos , Reação em Cadeia da Polimerase Multiplex , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Micobactérias não Tuberculosas/isolamento & purificação , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Tuberculose/microbiologia
19.
Lung Cancer ; 139: 151-156, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805443

RESUMO

OBJECTIVES: Recent practice guidelines recommend endosonography for patients with radiological N0 non-small cell lung cancer (NSCLC) when the primary tumors are >3 cm in diameter or centrally located. However, any role for endosonography remains debatable. We evaluated the utility of endosonography in patients with radiological N0 NSCLC based on tumor centrality, diameter and histology. MATERIALS AND METHODS: Patients who underwent staging endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) for radiological N0 NSCLC were retrospectively investigated using prospectively collected endosonography data. The radiological N0 stage was defined by node diameter as evident on computed tomography images and 18F-FDG uptake using integrated positron emission tomography-computed tomography. RESULTS: In total of 168 patients, the median size of the primary tumor was 39 mm, and 41 % of tumors were centrally located. The prevalence of occult mediastinal metastases was 11.3 % (19/168). The sensitivity of endosonography in terms of diagnosing occult mediastinal metastases was only 47 % (9/19); 6 of 10 patients with false-negative endosonography data exhibited metastases in accessible nodes. The diagnostic performance of endosonography did not differ by tumor centrality or diameter. Patients with adenocarcinoma histology showed higher prevalence of occult mediastinal metastases and higher false-negative results in endosonography compared with those with non-adenocarcinoma histology. CONCLUSION: Not all patients with radiological N0 NSCLC benefit from endosonography, given the low prevalence of occult mediastinal metastases and the poor sensitivity of endosonography in this population. The strategy of invasive mediastinal staging needs to be tailored considering the histology of the tumor in this population.

20.
J Clin Med ; 8(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703283

RESUMO

BACKGROUND: Limited data are available regarding the detailed characteristics and outcomes of surgically resected nontuberculous mycobacterial (NTM) granulomas. METHODS: We evaluated the characteristics of 49 NTM granulomas presenting as solitary pulmonary nodules (SPNs) between January 2007 and December 2016. RESULTS: Twenty-five patients (51%) were male and 27 (55%) were never-smokers. Seven (14%) patients had a history of tuberculosis. More than half (51%) of patients were asymptomatic. On chest computed tomography, the median SPN diameter was 18 mm, and approximately half of all SPNs (49%) were located in the upper lobes on chest computed tomography. NTM strain were preoperatively isolated from sputum (46%, 12/26), bronchial wash fluid (54%, 14/26), and needle biopsy specimens (12%, 3/26). Mycobacterium avium (71%, 22/31) was the organism most commonly isolated, followed by Mycobacterium intracellulare (16%, 5/31). Postoperative pneumothorax and atelectasis developed in four (8%) patients and one (2%) patient, respectively. Five patients received postoperative antibiotic therapy. Over a median follow-up period of 18.0 months, one patient with residual lesions after surgery started macrolide-based therapy due to aggravated symptoms. CONCLUSIONS: Most NTM granulomas can be treated completely by surgical resection without antibiotic therapy, and microbiological examination of surgical specimens is important for optimal management.

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