Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713

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Year 2019 - Volume 45  - Number 2  (March/April)

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Editorial

1 - Tuberculosis series 2019

Série tuberculose 2019

Denise Rossato Silva1,a, Giovanni Battista Migliori2,b, Fernanda Carvalho de Queiroz Mello3,c

J Bras Pneumol.2019;45(2):e20190064

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2 - Management and outcomes of severe childhood tuberculosis in the pediatric intensive care setting: can we identify best practices?

Tratamento e desfechos da tuberculose grave em crianças na unidade de terapia intensiva pediátrica: é possível identificar as melhores práticas?

Svetlana Velizarova1,a, Natalia Gabrovska1,b, Albena Spasova1,c, Ben Marais2,3,d, Elizabeth Page Harausz4,e, Simon Tiberi5,6,f, Giovanni Battista Migliori7,g, Davide Manissero8,h

J Bras Pneumol.2019;45(2):e20190043

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Continuing Education: Imaging

3 - Nodular reversed halo sign

Sinal do halo invertido nodular

Edson Marchiori1,a, Bruno Hochhegger2,b, Gláucia Zanetti1,c

J Bras Pneumol.2019;45(2):e20180335

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Original Article

6 - Primary bacillary resistance in multidrug-resistant tuberculosis and predictive factors associated with cure at a referral center in São Paulo, Brazil

Resistência bacilar primária em tuberculose multidrogarresistente e fatores preditivos associados à cura, em um centro de referência da cidade de São Paulo

Marcia Telma Guimarães Savioli1,a, Nelson Morrone2,b, Ilka Santoro1,c

J Bras Pneumol.2019;45(2):e20180075

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Objective: To identify transmitted or primary resistance among cases of multidrug-resistant tuberculosis and predictive factors for cure in multidrug-resistant tuberculosis after the first treatment. Method: Descriptive study of a cohort from 2006 to 2010, in a reference unit of tuberculosis in São Paulo, Brazil. The data were obtained by the revision of medical records. Clinical criteria were used to classify transmitted and acquired resistance. Extended primary resistance was also defined, in this study, as cases initially treated with a standardized scheme, but with no therapeutic success, and the pre-treatment drug susceptibility test (DST) showed presence of resistance. Results: 156 patients with multidrug-resistant tuberculosis and their respective sputum samples were eligible for the study. Only 7% of the patients were positive for the human immunodeficiency virus (HIV). Previous treatment occurred in 95% of the sample. The cure rate after the first treatment was 54%. The median bacteriological conversion time of those who healed was one month. Bacillary resistance was considered acquired resistance in 100 (64%) and transmitted resistance in 56 (36%). By logistic regression, patients who presented primary multidrug-resistant tuberculosis (odds ratio-OR = 6,29), without comorbidity (OR = 3,37) and with higher initial weight (OR = 1.04) were associated with cure after the first treatment. Conclusion: The early detection of bacillary resistance and appropriate treatment are in favor of healing. Thus, it is crucial to know exactly the primary resistance rate avoiding the use of inadequate treatments, amplification of bacillary resistance and its transmission.

 


Keywords: Multidrug-resistant tuberculosis; Drug resistance; Treatment outcome.

 

7 - Smoking and pulmonary tuberculosis treatment failure: a case-control study

Tabaquismo y fracaso del tratamiento de la tuberculosis pulmonar. Un estudio de casos y controles

Juan Pablo Aguilar1,a, María B Arriaga2,3,b, Monica Ninet Rodas1,4,c, Eduardo Martins Netto1,3,5,d

J Bras Pneumol.2019;45(2):e20180359

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Objective: To determine the association between smoking and pulmonary tuberculosis treatment failure. Methods: This was a case-control study conducted at the Brazilian Institute for Tuberculosis Research in the city of Salvador, Brazil, between 2007 and 2015. We evaluated 284 patients treated for pulmonary tuberculosis, comparing 50 cases of treatment failure with 234 control cases in which the final outcome was cure. Results: Treatment failure was attributed to smoking and age rather than to gender, income, level of education, alcohol consumption, or marital status. Therefore, even after adjustment for age, the risk of treatment failure was 2.1 times (95% CI: 1.1-4.1) higher among the patients with a history of smoking. In addition, being over 50 years of age was found to increase the likelihood of treatment failure by 2.8 times (95% CI: 1.4-6.0). Conclusions: Smoking and aging are both associated with pulmonary tuberculosis treatment failure. Therefore, as part of a tuberculosis control program, health personnel should be prepared to offer strategies to promote smoking cessation and should be more careful with older patients.

 


Keywords: Tobacco use disorder; Tuberculosis; Treatment failure.

 

8 - Pulmonary nontuberculous mycobacterial infections: presumptive diagnosis based on the international microbiological criteria adopted in the state of São Paulo, Brazil, 2011-2014

Micobacterioses pulmonares: diagnóstico presuntivo pelos critérios microbiológicos internacionais adotados no estado de São Paulo, Brasil, 2011-2014

Lilian Regina Macelloni Marques1,a, Lucilaine Ferrazoli2,b, Érica Chimara2,c

J Bras Pneumol.2019;45(2):e20180278

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Objective: Pulmonary nontuberculous mycobacterial infections are caused by nontuberculous mycobacteria (NTM), the microbiological diagnosis of which involves the isolation and identification of the same species in at least two sputum samples, one BAL fluid sample, or one lung biopsy sample. The objective of the present study was to determine the frequency at which the various NTM species are identified among selected individuals and in potential cases of pulmonary nontuberculous mycobacterial infection. Methods: This was a retrospective analysis of the data on species isolated from respiratory specimens collected from 2,843 individuals between 2011 and 2014. Potential NTM infection cases were identified on the basis of the international microbiological criteria adopted in the state of São Paulo. Results: A total of 50 species were identified using the molecular method PCR-restriction enzyme analysis. Samples collected from 1,014 individuals were analyzed in relation to the microbiological criteria, and 448 (44.18%) had a presumptive diagnosis of pulmonary nontuberculous mycobacterial infection, the species identified most frequently being, in descending order, Mycobacterium kansasii, M. abscessus, M. intracellulare, M. avium, and M. szulgai. Conclusions: Although various NTM species were identified among the individuals studied, those presumptively identified most frequently on the basis of the microbiological criteria adopted in the state of São Paulo were the ones that are most commonly associated with pulmonary nontuberculous mycobacterial infection worldwide or in specific geographic regions.

 


Keywords: Nontuberculous mycobacteria/classification; Mycobacterium infections, nontuberculous/diagnosis; Lung.

 

9 - Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing

Desempenho de testes para o diagnóstico de tuberculose pulmonar em populações indígenas no Brasil: a contribuição do Teste Rápido Molecular

Jocieli Malacarne1,a, Alexsandro Santos Heirich2,b, Eunice Atsuko Totumi Cunha3,c, Ida Viktoria Kolte4,d, Reinaldo Souza-Santos4,e, Paulo Cesar Basta4,f

J Bras Pneumol.2019;45(2):e20180185

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Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

 


Keywords: Tuberculosis; Molecular diagnostic testing; Diagnostic tests, routine; Indians, South American.

 

10 - Treatment compliance of patients with paracoccidioidomycosis in Central-West Brazil

Adesão ao tratamento de pacientes com paracoccidioidomicose na Região Centro-Oeste do Brasil

Ursulla Vilella Andrade1,a, Sandra Maria do Valle Leone de Oliveira1,b, Marilene Rodrigues Chang1,c, Edy Firmina Pereira1,d, Ana Paula da Costa Marques1,e, Lidia Raquel de Carvalho2,f, Rinaldo Poncio Mendes2,g, Anamaria Mello Miranda Paniago1,h

J Bras Pneumol.2019;45(2):e20180167

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Objective: To evaluate the treatment compliance of patients with paracoccidioidomycosis. Methods: We studied 188 patients with paracoccidioidomycosis admitted to a tertiary referral hospital in the Central-West Region of Brazil from 2000 to 2010, to assess their compliance to treatment. In order to be considered compliant, patients needed to present two established criteria: (1) receive medicines from the pharmacy, and (2) achieve a self-reported utilization of at least 80% of the dispensed antifungal compounds prescribed since their previous appointment. Results: Most patients were male (95.7%), had the chronic form of the disease (94.2%), and were treated with cotrimoxazole (86.2%). Only 44.6% of patients were treatment compliant. The highest loss to follow-up was observed in the first 4 months of treatment (p < 0.02). Treatment compliance was higher for patients with than for those without pulmonary involvement (OR: 2.986; 95%CI 1.351-6.599), and higher for patients with than without tuberculosis as co-morbidity (OR: 2.763; 95%CI 1.004-7.604). Conclusions: Compliance to paracoccidioidomycosis treatment was low, and the period with the highest loss to follow-up corresponds to the first four months. Pulmonary paracoccidioidal involvement or tuberculosis comorbidity predicts a higher compliance to paracoccidioidomycosis therapy.

 


Keywords: Paracoccidioidomycosis; Treatment adherence and compliance; loss to follow-up; mycoses

 

11 - Speeding up the diagnosis of multidrug-resistant tuberculosis in a high-burden region with the use of a commercial line probe assay

Agilizando o diagnóstico da tuberculose multirresistente em uma região endêmica com o uso de um teste comercial de sondas em linha

Angela Pires Brandao1,2,a, Juliana Maira Watanabe Pinhata1,b, Rosangela Siqueira Oliveira1,c, Vera Maria Neder Galesi3,d, Helio Hehl Caiaffa-Filho1,e, Lucilaine Ferrazoli1,f

J Bras Pneumol.2019;45(2):e20180128

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Objective: To evaluate the rapid diagnosis of multidrug-resistant tuberculosis, by using a commercial line probe assay for rifampicin and isoniazid detection (LPA-plus), in the routine workflow of a tuberculosis reference laboratory. Methods: The LPA-plus was prospectively evaluated on 341 isolates concurrently submitted to the automated liquid drug susceptibility testing system. Results: Among 303 phenotypically valid results, none was genotypically rifampicin false-susceptible (13/13; 100% sensitivity). Two rifampicin-susceptible isolates harboured rpoB mutations (288/290; 99.3% specificity) which, however, were non-resistance-conferring mutations. LPA-plus missed three isoniazid-resistant isolates (23/26; 88.5% sensitivity) and detected all isoniazid-susceptible isolates (277/277; 100% specificity). Among the 38 (11%) invalid phenotypic results, LPA-plus identified 31 rifampicin- and isoniazid-susceptible isolates, one isoniazid-resistant and six as non-Mycobacterium tuberculosis complex. Conclusions: LPA-plus showed excellent agreement (≥91%) and accuracy (≥99%). Implementing LPA-plus in our setting can speed up the diagnosis of multidrug-resistant tuberculosis, yield a significantly higher number of valid results than phenotypic drug susceptibility testing and provide further information on the drug-resistance level.

 


Keywords: Tuberculosis, multidrug-resistant; Molecular diagnostic techniques; Microbial sensitivity tests; Mycobacterium tuberculosis.

 

Brief Communication

12 - Accuracy of a rapid molecular test for tuberculosis in sputum samples, bronchoalveolar lavage fluid, and tracheal aspirate obtained from patients with suspected pulmonary tuberculosis at a tertiary referral hospital

Acurácia do teste rápido molecular para tuberculose em amostras de escarro, lavado broncoalveolar e aspirado traqueal obtidos de pacientes com suspeita de tuberculose pulmonar em um hospital de referência terciária

Tatiane Maria da Silva1,a, Valéria Martins Soares2,b, Mariana Gontijo Ramos1,c, Adriana dos Santos1,d

J Bras Pneumol.2019;45(2):e20170451

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Tuberculosis continues to be a major public health problem worldwide. The aim of the present study was to evaluate the accuracy of the Xpert MTB/RIF rapid molecular test for tuberculosis, using pulmonary samples obtained from patients treated at the Júlia Kubitschek Hospital, which is operated by the Hospital Foundation of the State of Minas Gerais, in the city of Belo Horizonte, Brazil. This was a retrospective study comparing the Xpert MTB/RIF test results with those of standard culture for Mycobacterium tuberculosis and phenotypic susceptibility tests. Although the Xpert MTB/RIF test showed high accuracy for the detection of M. tuberculosis and its resistance to rifampin, attention must be given to the clinical status of the patient, in relation to the test results, as well as to the limitations of molecular tests.

 


Keywords: Tuberculosis/diagnosis; Molecular diagnostic techniques; Sputum; Bronchoalveolar lavage fluid.

 

13 - Trends in tuberculosis mortality in Brazil (1990-2015): joinpoint analysis

Tendência da mortalidade por tuberculose no Brasil (1990-2015): análise por pontos de inflexão

Carlos Dornels Freire de Souza1,a, João Paulo Silva de Paiva1,b, Leonardo Feitosa da Silva1,c, Thiago Cavalcanti Leal1,d, Mônica de Avelar Figueiredo Mafra Magalhães2,e

J Bras Pneumol.2019;45(2):e20180393

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The objective of this study was to analyze trends in the tuberculosis mortality rate in Brazil (1990-2015) in an ecological time-series analysis. The indicators were obtained from the Brazilian National Ministry of Health. A joinpoint regression model was applied for the temporal analysis, with a level of significance of 5%. During the period in question, there was a trend toward a reduction in mortality in the country as a whole (p < 0.001) and in each of its five regions. The states with the highest tuberculosis mortality rates were Rio de Janeiro (7.0/100,000 population) and Pernambuco (5.0/100,000 population). Eleven states and the Federal District of Brasília showed downward trends. Only the state of Alagoas showed a significant increase (p < 0.001). The temporal behavior observed indicates that tuberculosis continues to be a major public health problem in Brazil.

 


Keywords: Tuberculosis/epidemiology; Tuberculosis/mortality; Mortality/trends; Epidemiologic studies.

 

Review Article

14 - International collaboration among medical societies is an effective way to boost Latin American production of articles on tuberculosis

A colaboração internacional entre sociedades médicas é uma forma eficaz de aumentar a produção de artigos sobre tuberculose na América Latina

Giovanni Battista Migliori1,a, Rosella Centis1,b, Lia D'Ambrosio2,c, Denise Rossato Silva3,d, Adrian Rendon4,e

J Bras Pneumol.2019;45(2):e20180420

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Objective: Most studies of tuberculosis originate from high-income countries with a low incidence of tuberculosis. A review of the scientific production on tuberculosis in Latin American countries, most of which are low- or middle-income countries (some with high or intermediate tuberculosis incidence rates), would improve the understanding of public health challenges, clinical needs, and research priorities. The aims of this systematic review were to determine what has been published recently in Latin America, to identify the leading authors involved, and to quantify the impact of international collaborations. Methods: We used PubMed to identify relevant manuscripts on pulmonary tuberculosis (PTB), drug-resistant tuberculosis (DR-TB), or multidrug-resistant tuberculosis (MDR-TB), published between 2013 and 2018. We selected only studies conducted in countries with an annual tuberculosis incidence of ≥ 10,000 reported cases and an annual MDR-TB incidence of ≥ 300 estimated cases, including Brazil, Peru, Mexico, Colombia, and Argentina. Articles were stratified by country, type, and topic. Results: We identified as eligible 395 studies on PTB and 188 studies on DR/MDR-TB-of which 96.4% and 96.8%, respectively, were original studies; 35.5% and 32.4%, respectively, had an epidemiological focus; and 52.7% and 36.2%, respectively, were conducted in Brazil. The recent Latin American Thoracic Association/European Respiratory Society/Brazilian Thoracic Association collaborative project boosted the production of high-quality articles on PTB and DR/MDR-TB in Latin America. Conclusions: Most of the recent Latin American studies on tuberculosis were conducted in Brazil, Mexico, or Peru. Collaboration among medical societies facilitates the production of scientific papers on tuberculosis. Such initiatives are in support of the World Health Organization call for intensified research and innovation in tuberculosis.

 


Keywords: Tuberculosis, pulmonary; Tuberculosis, multidrug-resistant; Latin America.

 

15 - Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation

Tratamento da tuberculose grave e suas sequelas: da terapia intensiva à cirurgia e reabilitação

Simon Tiberi1,2,a, Marcela Muñoz Torrico3,b, Ananna Rahman1,c, Maria Krutikov1,d, Dina Visca4,e, Denise Rossato Silva5,f, Heinke Kunst2,g, Giovanni Battista Migliori4,h

J Bras Pneumol.2019;45(2):e20180324

Abstract PDF PT PDF EN Portuguese Text

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

 


Keywords: Extensively drug-resistant tuberculosis; Tuberculosis, multidrug-resistant; Critical care; Smoking cessation.

 

16 - Latent tuberculosis infection in patients with rheumatic diseases

Infecção latente por tuberculose em pacientes com doenças reumatológicas

Camila Anton1,2,a, Felipe Dominguez Machado1,2,b, Jorge Mario Ahumada Ramirez1,2,c, Rafaela Manzoni Bernardi1,2,d, Penélope Esther Palominos3,e, Claiton Viegas Brenol3,f, Fernanda Carvalho de Queiroz Mello4,g, Denise Rossato Silva1,2,h

J Bras Pneumol.2019;45(2):e20190023

Abstract PDF PT PDF EN Portuguese Text

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.

 


Keywords: Tuberculosis; Latent tuberculosis; Tuberculin skin test; Anti-TNF therapy; Tumor necrosis factor-alpha; Rheumatoid arthritis.

 

Images in Pulmonary Medicine

Letters to the Editor

19 - Serum pyrazinamide concentrations in patients with pulmonary tuberculosis

Níveis sanguíneos de pirazinamida no tratamento da tuberculose pulmonar

Stefania de Medeiros Araujo Lucena1,a, Carlos Augusto Abreu Alberio2,b, Ana Carla Godinho Pinto3,c, José Luiz Fernandes Vieira2,4,d

J Bras Pneumol.2019;45(2):e20180254

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20 - Palmar telangiectasia is associated with the intensity of smoking

Telangiectasia palmar está associada à intensidade do tabagismo

Dragica Petar Pesut1,2,a, Ana Milan Samardzic2,b, Milica Vojin Bulajic3,c, Tijana Tatjana Cvok-Debeljak2,d

J Bras Pneumol.2019;45(2):e20180273-e2018273

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Author's reply

22 - Authors' reply - Reflections on the article "Correlation of lung function and respiratory muscle strength with functional exercise capacity in obese individuals with obstructive sleep apnea syndrome"

Resposta dos autores sobre o artigo Reflexões sobre o artigo

Thays Maria da Conceição Silva Carvalho1,a, Anísio Francisco Soares2,b, Danielle Cristina Silva Climaco3,c, Isaac Vieira Secundo3,d, Anna Myrna Jaguaribe de Lima2,e

J Bras Pneumol.2019;45(2):e20180327

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