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Ricardo LM Duarte,1,2 Flavio J Magalhães-da-Silveira,1 Tiago S Oliveira-e-Sá,3,4 Joana A Silva,5 Fernanda CQ Mello,2 David Gozal6 1Sleep - Laboratório de Estudo dos Distúrbios do Sono, Centro Médico BarraShopping, Rio de Janeiro, Brazil; 2Instituto de Doenças do Tórax, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 3Hospital de Santa Marta, Centro Hospitalar Lisboa Central, Lisbon, Portugal; 4NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal; 5Clínica São Vicente, Rede D’Or, Rio de Janeiro, Brazil; 6Department of Child Health, University of Missouri School of Medicine, Columbia, MO, USACorrespondence: David GozalDepartment of Child Health, University of Missouri School of Medicine, Columbia, MO, USAEmail drdavidgozal@gmail.comBackground: Obstructive sleep apnea (OSA) is a very prevalent disorder. Here, we aimed to develop and validate a practical questionnaire with yes-or-no answers, and to compare its performance with other well-validated instruments: No-Apnea, STOP-Bang, and NoSAS.Methods: A cross-sectional study containing consecutively selected sleep-lab subjects underwent full polysomnography. A 4-item model, named GOAL questionnaire (gender, obesity, age, and loud snoring), was developed and subsequently validated, with item-scoring of 0– 4 points (≥ 2 points indicating high risk for OSA). Discrimination was assessed by area under the curve (AUC), while predictive parameters were calculated using contingency tables. OSA severity was classified based on conventionally accepted apnea/hypopnea index thresholds: ≥ 5.0/h (OSA≥ 5), ≥ 15.0/h (OSA≥ 15), and ≥ 30.0/h (OSA≥ 30).Results: Overall, 7377 adults were grouped into two large and independent cohorts: derivation (n = 3771) and validation (n = 3606). In the derivation cohort, screening of OSA≥ 5, OSA≥ 15, and OSA≥ 30 revealed that GOAL questionnaire achieved sensitivity ranging from 83.3% to 94.0% and specificity ranging from 62.4% to 38.5%. In the validation cohort, screening of OSA≥ 5, OSA≥ 15, and OSA≥ 30, corroborated validation steps with sensitivity ranging from 83.7% to 94.2% and specificity from 63.4% to 37.7%. In both cohorts, discriminatory ability of GOAL questionnaire for screening of OSA≥ 5, OSA≥ 15, and OSA≥ 30 was similar to No-Apnea, STOP-Bang or NoSAS.Conclusion: All four instruments had similar performance, leading to a possible greater practical implementation of the GOAL questionnaire, a simple instrument with only four parameters easily obtained during clinical evaluation.Keywords: obstructive sleep apnea, polysomnography, screening, questionnaire, diagnosis

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

© 2016 Conde et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.B

BACKGROUND: Tuberculosis (TB) remains as an important public health problem worldwide. The most common type is pulmonary TB, and the most prevalent form of extra-pulmonary disease among HIV-negative patients is pleural disease. OBJECTIVE: The objective of the present study was to determine the effect of continuous positive airway pressure (CPAP) on fluid absorption among patients with pleural effusion due to TB. METHODS: Twenty patients were randomized into two groups. The interventional group (n=10) received CPAP three times a week during the initial four weeks of anti-TB treatment, and the control group (n=10) received anti-TB drugs only. The primary endpoint was the volume of pleural fluid after four weeks of treatment. Both groups were submitted to thoracic computed tomography using three-dimensional image reconstruction. The Mann-Whitney test for independent samples and the Wilcoxon paired samples test were used for statistical analysis. The normal distribution samples were analyzed using the unpaired t test. RESULTS: The reduction of pleural effusion volume was significantly greater in the intervention group (83.5%±SD 3.6) than in the control group (36.9%±SD 2.9; p<0.001), and the final dyspnea index was lower in the Intervention group than in the control group (p=0.002). CONCLUSION: Our findings indicate that CPAP during the first month of TB treatment accelerates the absorption of pleural effusion, however, additional studies are needed to confirm these findings and evaluate the impact of CPAP on pleural sequelae after the end of anti-TB treatment. Article registered in the Clinical Trials under the number NCT00560521. [ABSTRACT FROM AUTHOR]

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro., Methods: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges., Results: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%., Conclusions: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.

Purpose: To evaluate the prevalence and potential predictors of obstructive sleep apnea (OSA) in a cohort of adults with severe asthma., Methods: From March 2021 to December 2021, this cross-sectional study enrolled patients with severe asthma receiving biologics, who were consecutively referred for sleep evaluation irrespective of sleep-related symptoms. Clinical and functional data, including three OSA screening instruments (GOAL, STOP-Bang, and NoSAS) were recorded. All participants underwent a portable sleep test (ApneaLink Air™). OSA diagnosis was based on the respiratory disturbance index ≥ 5.0/h and subclassified according to severity thresholds. Data were subjected to logistic regression tests to identify possible predictors for OSA. Discrimination was estimated from the area under the curve (AUC)., Results: Overall, 56 outpatients were included (80% females): 54% with any OSA, 13% with moderate-to-severe OSA, and 4% with severe OSA. In the multivariate analysis, no parameter emerged as an independent predictor for OSA: age (p = 0.080), body mass index (p = 0.060), loud snoring (p = 0.130), and hypertension (p = 0.848). No screening instrument was useful to predict any OSA: GOAL (AUC: 0.714; 95% confidence interval (CI): 0.579-0.849), NoSAS (AUC: 0.645; 95% CI: 0.497-0.793), and STOP-Bang (AUC: 0.640; 95% CI: 0.493-0.788). Similarly, no screening tool was also useful for predicting moderate-to-severe OSA or severe OSA., Conclusion: Patients with evere asthma receiving biologics exhibit a high prevalence of OSA. However, no clinical, functional, or OSA screening instrument showed acceptable discriminatory ability to predict the presence of OSA in these patients with severe asthma., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.

Purpose: To evaluate the frequency of sleep-disordered breathing (SDB) and predictors of the presence of nocturnal desaturation in adults with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension., Methods: Outpatients with a hemodynamic diagnosis of precapillary pulmonary hypertension who underwent portable polysomnography were evaluated. Diagnosis and severity of SDB were assessed using three well-established respiratory disturbance index (RDI) thresholds: 5.0/h, 15.0/h, and 30.0/h, while nocturnal hypoxemia was defined by the average oxygen saturation (SpO 2 ) < 90%. Multiple linear regression analysis evaluated the potential relationships among explanatory variables with the dependent variable (average SpO 2 values), with comparisons based on the standardized regression coefficient (β). The R-squared (R 2 ; coefficient of determination) was used to evaluate the goodness-of-fit measure for the linear regression model., Results: Thirty-six adults were evaluated (69.4% females). The majority of the participants (75.0%) had SDB (26 with obstructive sleep apnea [OSA] and one with central sleep apnea [CSA]); while 50% of them had nocturnal hypoxemia. In the linear regression model (R 2  = 0.391), the mean pulmonary artery pressure [mPAP] (β - 0.668; p = 0.030) emerged as the only independent parameter of the average SpO 2 ., Conclusion: Our study found that the majority of the participants had some type of SDB with a marked predominance of OSA over CSA, while half of them had nocturnal desaturation. Neither clinical and hemodynamic parameters nor the RDI was a predictor of nocturnal desaturation, except for mPAP measured during a right heart catheterization, which emerged as the only independent and significant predictor of average SpO 2 ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort., Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed., Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge., Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge., Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ., Competing Interests: Estevão Portela Nunes has received payment for lectures by Gilead; Alexandre Vargas Schwarzbold has received grants from AZ, MSD and Clover Biopharm; Fernanda Carvalho de Queiroz Mello has been acting as the President of the Society of Pneumonology and Tisiology fo the State of Rio de Janeiro (no payment) and Beatriz Grinsztejn has been participating in Advisory Board of Merck; GSK/ViiV and Janssen; The other authors declare no conflicts of interest., (© 2022 The Author(s).)

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

On April 1st, 2020, COVID-19 surpassed tuberculosis regarding the number of deaths per day worldwide. The combination of tuberculosis and COVID-19 has great potential for morbidity and mortality. In addition, the COVID-19 pandemic has had a significant impact on the diagnosis and treatment of tuberculosis. In this review article, we address concurrent tuberculosis and COVID-19, with particular regard to the differences between Brazil and Europe. In addition, we discuss priorities in clinical care, public health, and research.

Introduction: Laboratory and clinical features of childhood tuberculosis (TB) are non-specific and establishing an accurate diagnosis remains a challenge. This study evaluated a Single tube nested-PCR (STNPCR) to detect genomic DNA of Mycobacterium tuberculosis complex in blood and urine., Methods: Biological samples were obtained from children (<15 years old) with clinical suspicion of pulmonary and extrapulmonary TB at public hospitals in Recife-Pernambuco, Brazil. Cultures yielded negative results in a majority of childhood TB cases, which are generally paucibacillary. A set of clinical, epidemiological, radiological, and laboratory criteria with evident clinical improvement after anti-TB treatment were frequently used to define childhood TB cases., Results: Ninety children with clinical suspicion were enrolled in this study (44 with TB and 46 without TB). The pulmonary TB group had 20 confirmed cases and 46 negative controls, while the extrapulmonary TB group had 24 confirmed cases. The STNPCR showed sensitivities to pulmonary and extrapulmonary TB of 47.4% and 52.2% (blood) and 38.8% and 20% (urine), respectively. Considering the low performance of STNPCR on separate samples, we decided to perform a combined analysis (parallel sensitivity analysis) of the results from blood and urine samples. The parallel sensitivity increased to 65% in blood and 62.5% in urine. The specificity in both samples ranged from 93.5-97.8%., Conclusions: Although STNPCR showed moderate sensitivity, the specificity is high; therefore, the test can be used as an auxiliary tool to diagnose TB in children. It is a rapid test that demonstrated better performance than other diagnostic tests in paucibacillary samples as it does in childhood tuberculosis.

Objective: To evaluate the performance of the No-Apnea score, a simplified screening instrument for obstructive sleep apnea (OSA), by gender., Methods: This was a cross-sectional study including adults undergoing full polysomnography. The No-Apnea model comprises two items (neck circumference and age) with a total score of 0 to 9. The severity of OSA was categorized, on the basis of the apnea-hypopnea index, as any (≥ 5 events/h), moderate-to-severe (≥ 15 events/h), or severe (≥ 30 events/h). The performance of the No-Apnea instrument was assessed by determining the area under the (ROC) curve (AUC) and by constructing contingency tables., Results: We evaluated a total of 6,606 adults (53.8% men). For categorizing the level of OSA severity, the No-Apnea score had a sensitivity of 83.9-93.0% and a specificity of 57.3-35.2%. At all OSA severity levels, the No-Apnea score exhibited higher sensitivity and lower specificity in men than in women. The No-Apnea score proved to be an appropriate screening model for patients in general or when separated by gender or severity of OSA (AUC > 0.7 for all). The discriminatory power of the No-Apnea score to predict any, moderate-to-severe, and severe OSA was similar between genders (p = 0.109, p = 0.698, and p = 0.094, respectively)., Conclusions: In a sample of adults referred to the sleep laboratory, there was no significant difference between men and women in terms of the discriminatory power of the No-Apnea instrument in for screening for OSA severity.

Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

Objective: To compare patients with and without previous lung disease, in terms of the spirometry results after they had been treated for pulmonary tuberculosis (PTB) and cured, as well as to analyze risk factors related to functional severity., Methods: This was a cross-sectional, multicenter study conducted at four referral centers in Brazil. Patients were divided into two groups: those with a history of lung disease or smoking (LDS+ group); and those with no such history (LDS- group). Patients underwent spirometry (at least six months after being cured). Sociodemographic and clinical data were collected., Results: A total of 378 patients were included: 174 (46.1%) in the LDS+ group and 204 (53.9%) in the LDS- group. In the sample as a whole, 238 patients (62.7%) had spirometric changes. In the LDS+ group, there was a predominance of obstructive lung disease (in 33.3%), whereas restrictive lung disease predominated in the LDS- group (in 24.7%). Radiological changes were less common in the LDS- group than in the LDS+ group (p < 0.01), as were functional changes (p < 0.05). However, of the 140 (79.1%) LDS- group patients with a normal or minimally altered chest X-ray, 76 (54%) had functional changes (p < 0.01). The risk factors associated with functional severity in the LDS- group were degree of dyspnea (p = 0.03) and moderate or severe radiological changes (p = 0.01)., Conclusions: Impaired pulmonary function is common after treatment for PTB, regardless of the history of lung disease or smoking. Spirometry should be suggested for patients who develop moderate/severe dyspnea or relevant radiological changes after treatment for PTB.

Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.

In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB ( n  = 8), latent TB infection (LTBI; n  = 21), and treated LTBI (LTBItt; n  = 6) and in uninfected exposed controls (ExC; n  = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like ( P  = 0.03) but not M1-like ( P  = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB. IMPORTANCE Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection., (Copyright © 2019 de Araujo et al.)

Purpose: Obstructive sleep apnea (OSA) is very common occurrence among morbidly obese patients. Our main objectives were to validate the No-Apnea, a 2-item screening tool, in morbidly obese patients and compare its performance with three other instruments: STOP-Bang questionnaire, NoSAS score, and Epworth Sleepiness Scale (ESS)., Methods: A cross-sectional analysis of morbidly obese patients (body mass index [BMI] ≥ 35.0 kg/m 2 ) grouped into two independent samples: bariatric surgery patients (BS) and non-bariatric surgery patients (NBS). All patients underwent overnight polysomnography. Discriminatory ability was assessed by area under the curve (AUC). OSA severity was defined by apnea/hypopnea index cut-off points: ≥ 5.0/h (OSA ≥5 ), ≥ 15.0/h (OSA ≥15 ), and ≥ 30.0/h (OSA ≥30 )., Results: A total of 1017 subjects (40.4% in BS cohort and 59.6% in NBS cohort) were evaluated. In the BS cohort, No-Apnea had similar discrimination to STOP-Bang and NoSAS for predicting OSA ≥5 (p = 0.979 and p = 0.358, respectively), OSA ≥15 (p = 0.158 and p = 0.399, respectively), and OSA ≥30 (p = 0.388 and p = 0.903, respectively). In the NBS cohort, No-Apnea had similar discrimination to STOP-Bang and NoSAS for predicting OSA ≥5 (p = 0.528 and p = 0.428, respectively), OSA ≥15 (p = 0.825 and p = 0.108, respectively), and OSA ≥30 (p = 0.458 and p = 0.186, respectively). Moreover, No-Apnea performed significantly better than ESS in both BS and NBS cohorts (p < 0.001)., Conclusions: No-Apnea is a useful and practical tool for screening of OSA in morbidly obese patients, with non-inferior performance to STOP-Bang questionnaire and NoSAS score.

Objective  Lung cancer is the leading cause of death by cancer, and the bones are one of the most common sites of metastasis from this condition. This study aimed to evaluate the influence of lung carcinoma histology on the frequency of bone metastases. Methods  This retrospective study evaluated the medical records of 407 patients diagnosed with lung cancer between 2003 and 2012. The prevalence of bone metastases and their association with histological subtypes were evaluated using chi-squared tests, odds ratios (ORs) and 95% confidence intervals (CIs). The overall survival was evaluated using the Kaplan-Meier method. Results  The prevalence of bone metastases was 28.2% ( n  = 115), and the spine was the most frequently affected site (98 metastases; 32.1%). Adenocarcinoma was the most common histological subtype of lung carcinoma (46.7%), and it was significantly more frequent among patients with bone metastases (58.3% versus 42.1%; p  = 0.003; OR = 1.92; 95% CI: 1.29-2.97). Squamous cell carcinoma was significantly less frequent among patients with bone metastases (13.0% versus 29.8%; p  = 0.0004; OR = 0.35; 95% CI: 0.19-0.64). The median survival time after the first bone metastasis diagnosis was 4 months. Conclusion  Adenocarcinoma was the most common histological subtype of lung carcinoma, and it was significantly associated with a higher risk of developing bone metastases., Competing Interests: Conflitos de Interesse Os autores declaram não haver conflitos de interesse.

Purpose: Obstructive sleep apnea (OSA) and insomnia are very prevalent disorders, especially in sleep-lab setting, and insomnia may be the presenting complaint of OSA. Here, we aimed to validate No-Apnea as screening tool for OSA in patients with self-reported insomnia complaints and to compare its performance with other models., Methods: This cross-sectional study involved evaluation of No-Apnea as well as STOP-Bang, NoSAS and Epworth Sleepiness Scale (ESS) in subjects with insomnia being evaluated with full in-lab polysomnography. Discrimination was assessed by area under the curve (AUC), while predictive parameters were calculated by contingency tables. OSA severity was classified based on the apnea/hypopnea index: ≥ 5.0/h as any OSA (OSA ≥5 ), ≥ 15.0/h as moderate/severe OSA (OSA ≥15 ), and ≥ 30.0/h as severe OSA (OSA ≥30 )., Results: Overall, 2591 patients with a clinical diagnosis of insomnia were included. Diagnosis of OSA ≥5 , OSA ≥15 , and OSA ≥30 was of 76.3%, 53.1%, and 32.6%, respectively. At all levels of OSA severity, No-Apnea had sensitivity ranging from 84.5 to 94.1% and specificity ranging from 58.2 to 35.1%. For screening of OSA ≥5 , OSA ≥15 , and OSA ≥30 , discriminatory ability (AUC) of No-Apnea was: 0.790 [95% confidence interval (CI) 0.770-0.810], 0.758 (95% CI 0.740-0.777), and 0.753 (95% CI 0.734-0.772), respectively. Based on AUCs, No-Apnea, STOP-Bang, and NoSAS performed similar at all levels of OSA severity. The ESS did not present satisfactory discrimination as OSA screening model., Conclusions: In a large sample of patients with insomnia, No-Apnea, STOP-Bang, and NoSAS, but not ESS, enable satisfactory and similar discrimination at all levels of OSA severity.

Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.

Purpose: Obstructive sleep apnea (OSA) is a common condition characterized by repetitive collapse of the upper airways and intermittent oxygen desaturation, which may lead to airway inflammation. Here, we explored whether fractional exhaled nitric oxide (FeNO) levels provide a non-invasive screening tool of OSA., Methods: Over a 3-month period, FeNO levels were measured in consecutive non-smoking patients referred for a sleep laboratory. All patients underwent full polysomnography. OSA severity was classified based on the apnea/hypopnea index: ≥ 5.0/h as any OSA, ≥ 15.0/h as moderate/severe OSA, and ≥ 30.0/h as severe OSA. FeNO was measured by a portable device (NIOX-MINO®; Aerocrine AB, Solna, Sweden) and expressed as parts per billion (ppb). Discrimination by area under the curve (AUC) and binary logistic regression were performed., Results: A total of 229 subjects were evaluated. Mean FeNO values were similar among subjects without OSA or with OSA: 16.9 ± 10.6 ppb versus 20.2 ± 14.5 ppb, p = 0.221; respectively. FeNO was not an inclusionary parameter to predict any OSA, moderate/severe OSA, and severe OSA: odds ratio (OR) 1.023 (95% confidence interval [CI]: 0.986-1.062); OR 1.012 (95% CI: 0.991-1.034); and OR 0.999 (95% CI: 0.980-1.018), respectively. The AUC values for FeNO in the diagnosis of any OSA, moderate/severe OSA, and severe OSA showed no discriminatory properties: AUC: 0.567 (95% CI: 0.464-0.670), AUC: 0.541 (95% CI: 0.465-0.618), and AUC: 0.535 (95% CI: 0.459-0.610); respectively., Conclusions: In a sleep-lab setting, our findings suggest that FeNO measurements are inconsequential in the screening of OSA in adults.

Background: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is a condition with increasing morbidity, a more detailed knowledge of radiological aspects and pulmonary function plays a relevant role in the diagnosis and appropriate therapeutic management of these patients., Objectives: The purpose of this study was to evaluate changes in lung parenchyma through computed tomography (CT) densitometry and, secondarily, to analyze its correlation with pulmonary function testing (PFT) in patients with NTM-PD., Methods: This is a cross-sectional study in which 31 patients with NTM-PD and 27 controls matched by sex, age, and body mass index underwent CT pulmonary densitovolumetry and pulmonary function tests including spirometry and body plethysmograph., Results: Based on the total lung volume (TLV) and total lung mass (TLM) measurements, the cumulative mass ratios were calculated for 3% (M3), 15% (M15), 85% (M85), and 97% (M97) of the TLV. We also calculated the complement, which is represented by TLM (100%) minus the mass of 15% (C85) or 3% (C97) of the TLV. Patients with NTM-PD presented lower values of M3 and M15 than controls, with greater significant differences in the apical third and middle third measurements. Compared to controls, patients with NTM-PD showed higher values of C85 and C97, although significant differences were observed only in the basal third measurements. There were negative correlations of total lung capacity with M3 and M15 in the middle third and apical third measurements. There were positive correlations of residual volume and airway resistance with M3 at the apical third measurement., Conclusions: Patients with NTM-PD show reduced lung mass and increased lung mass in the apical and basal regions of the lungs, respectively. Furthermore, there is a relationship between lung mass measurements and pulmonary function parameters.

Study Objectives: To develop and validate a practical model for obstructive sleep apnea (OSA) screening in adults based on objectively assessed criteria, and then compare it with two widely used tools, namely STOP-BANG and NoSAS., Methods: This is a retrospective study of an existing database of consecutive outpatients who were referred for polysomnography for suspected sleep-disordered breathing by their primary care physicians. Area under the curve (AUC) and 2 × 2 contingency tables were employed to obtain the performance of the new instrument., Results: A total of 4,072 subjects were randomly allocated into two independent cohorts: one for derivation (n = 2,037) and one for validation (n = 2,035). A mnemonic model, named No-Apnea, with two variables (neck circumference and age) was developed (total score: 0-9 points). We used the cutoff ≥ 3 to classify patients at high risk of having OSA. OSA severity was categorized by apnea-hypopnea index (AHI): any OSA (AHI 5 ≥ events/h; OSA-5), moderate/ severe OSA (AHI 15 ≥ events/h; OSA-15); and severe OSA (AHI 30 ≥ events/h; OSA-30). In the derivation cohort, the AUCs for screening of OSA-5, OSA-15, and OSA-30 were: 0.784, 0.758, and 0.754; respectively. The rate of subjects correctly screened was 78.1%, 68.8%, and 54.4%, respectively for OSA-5, OSA-15, and OSA-30. Subsequently, the model was validated confirming its reproducibility. In both cohorts, No-Apnea discrimination was similar to STOP-BANG or NoSAS., Conclusions: The No-Apnea, a 2-item model, appears to be a useful and practical tool for OSA screening, mainly when limited resources constrain referral evaluation. Despite its simplicity when compared to previously validated tools (STOP-BANG and NoSAS), the instrument exhibits similar performance characteristics., (© 2018 American Academy of Sleep Medicine.)

Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.

Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions.

Objective: To evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay., Methods: In a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison., Results: A total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8-79.4%), including 97.9% (95% CI 96.4-99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6-52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9-99.6%). TB-LAMP test results were indeterminate in 0.3% of cases., Conclusions: TB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Despite the reported high heterogeneity of the human immune response to tuberculosis (TB), new studies may contribute to the understanding of Mycobacterium tuberculosis immunopathogenesis. To investigate the patterns of humoral response during latent (LTBI) and active TB, we evaluated specific IgG subclasses' response, by ELISA, to a set of mycobacterial antigens (Rv2029c, Rv2031c, Rv2034, Rv2628, Rv3353c ESAT6:CFP10, and the new chimeric PstS1 (285-374) :CFP10) in plasma samples from exposed uninfected controls (ExC, n = 24), LTBI (n = 61), and TB (n = 15) donors. In general, the TB group showed statistically higher levels of IgG1, and lower levels of IgG3. Keeping specificities ≥90%, the highest sensitivity for TB detection was observed for IgG1-ESAT6:CFP10 (93.3%), followed by IgG2-Rv3353 (86.7%), IgG1-Rv3353 (69.2%) and IgG1-PstS1 (285-374) :CFP10 (53.3%). The combinatory of high IgG1-ESAT6:CFP10, followed by low IgG2-Rv3353c titers increased the specificity for TB detection to 100%. Only IgG3-ESAT6:CFP10 showed statistical differences between ExC and LTBI, detecting 50% of the LTBI donors. For the first time, higher levels of IgG2-PstS1 (285-374) :CFP10 and IgG2-Rv3353 were observed in LTBI and ExC, as compared with a lower or absent immunoreactivity among TB. This study demonstrates differential modulation of subclasses' profiles for the stages of infection, which may contribute to the further development of new diagnostic tools., (Copyright © 2017 Elsevier Ltd. All rights reserved.)