RESUMO Objetivo: Avaliar a função pulmonar em uma coorte de pacientes com história de tuberculose pulmonar no Brasil, bem como avaliar o declínio da função pulmonar ao longo do tempo e compará-lo com o observado em coortes semelhantes no México e Itália. Métodos: As três coortes foram comparadas quanto à idade, tabagismo, testes de função pulmonar, teste de caminhada de seis minutos e gasometria arterial. Na coorte brasileira, os resultados dos testes de função pulmonar, do teste de caminhada de seis minutos e da gasometria arterial logo após o término do tratamento da tuberculose foram comparados com os obtidos no fim do período de acompanhamento. Resultados: As três coortes foram muito diferentes quanto aos resultados dos testes de função pulmonar. Os padrões ventilatórios mais comuns nas coortes brasileira, italiana e mexicana foram o padrão obstrutivo, o padrão misto e o padrão normal [em 58 pacientes (50,9%), em 18 pacientes (41,9%) e em 26 pacientes (44,1%), respectivamente]. Apenas 2 casos de tuberculose multirresistente foram incluídos na coorte brasileira, ao passo que na coorte mexicana foram incluídos 27 casos (45,8%). As médias da PaO2 e SaO2 foram mais baixas na coorte mexicana do que na brasileira (p < 0,0001 e p < 0,002 para PaO2 e SaO2, respectivamente). Na coorte brasileira, quase todos os parâmetros funcionais se deterioraram ao longo do tempo. Conclusões: Este estudo reforça a importância do tratamento precoce e eficaz de pacientes com tuberculose sensível, pois a tuberculose multirresistente aumenta o dano pulmonar. Quando o tratamento da tuberculose é concluído, os pacientes devem ser avaliados o quanto antes e, caso se estabeleça o diagnóstico de sequelas pulmonares da tuberculose, é preciso tratá-los e oferecer-lhes reabilitação pulmonar, pois há evidências de que ela é eficaz nesses pacientes.

ABSTRACT Objective: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

RESUMO A tuberculose continua a ser um importante problema de saúde para a humanidade. Embora os esforços para controlar a epidemia tenham reduzido sua mortalidade e incidência, há vários fatores predisponentes a ser controlados a fim de reduzir a carga da doença. Este artigo de revisão aborda alguns dos fatores de risco associados à infecção por tuberculose, como diabetes, tabagismo, uso de álcool e uso de outras drogas, que podem também contribuir para maus resultados do tratamento da tuberculose. A tuberculose pode levar a complicações no curso e no manejo de outras doenças, como o diabetes. Portanto, é importante identificar essas comorbidades em pacientes com tuberculose a fim de assegurar um manejo adequado de ambas as condições.

ABSTRACT 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.

Abstract Background: Th1/Th2 immunity is insufficient to control Mycobacterium tuberculosis (Mtb) infection, particularly against more virulent strains such as W-Beijing. Methods: Thirty patients with active tuberculosis (TBA) and 30 controls with latent tuberculosis (TBL) were included. The distribution of polymorphism rs2275913 was evaluated by real-time PCR. Mononuclear cells (MNCs) were stimulated with CFP-10 and ESAT-6 antigens and extracts of H37Rv, W-Beijing-HN878. Levels of IL-17, IFN-γ were quantified by Luminex. Differences were assessed with Student t and U of Mann-Whitney and p values < 0.05 were significant. Results: No significant association of the 197G>A polymorphism with susceptibility to TBA was found. An effect of the -197G>A mutation was observed on the IL-17A expression rate. The MNCs of TBA patients with A/G genotype showed higher IL-17A (185 pg/mL) production relative to G/G patients (100 pg/mL, p = 0.008). This was not observed in individuals with TBL. The antigens of H37Rv and HN878 stimulated higher production of IFN-γ in MNCs of patients with ATB (p < 0.05). Conclusion: The presence of the A allele at the -197 position of the IL-17A promoter conditions increased production of this cytokine in response to the W-Beijing-HN878 hypervirulent strain.

Resumen Antecedentes: La respuesta inmune Th1/Th2 es insuficiente para el control de la infección por Mycobacterium tuberculosis (Mtb), particularmente contra cepas más virulentas como W-Beijing. Métodos: Se incluyeron 30 pacientes con tuberculosis activa (TBA) y 30 controles con tuberculosis latente (TBL). Se evaluó la distribución del polimorfismo rs2275913 por PCR tiempo real. Se estimularon células mononucleares (CMN) con antígenos CFP-10 y ESAT-6 y extractos de H37Rv, W-Beijing-HN878. Los niveles de IL-17, IFN-γ se cuantificaron por Luminex. Las diferencias se evaluaron con t de Student y U de Mann-Whitney y valores de p < 0.05 fueron significativos. Resultados: No se encontró asociación significativa del polimorfismo-197G>A con la susceptibilidad a TBA. Se observó un efecto de la mutación -197G>A en la tasa de expresión de IL-17A. Las CMN de pacientes TBA con genotipo A/G mostraron una mayor producción de IL-17A (185 pg/mL) en relación con las de pacientes G/G (100 pg/mL, p = 0.008). Esto no se observó en individuos con TBL. Los antígenos de H37Rv y HN878 estimularon mayor producción de IFN-γ en CMN de pacientes con TBA (p < 0.05). Conclusión: La presencia del alelo A en la posición -197 del promotor de IL-17A condiciona mayor producción de esta citocina en respuesta a la cepa hipervirulenta W-Beijing-HN878.

RESUMO O papel da tuberculose como uma prioridade de saúde pública e a disponibilidade de ferramentas diagnósticas para avaliar o estado funcional (espirometria, pletismografia e DLCO), a gasometria arterial, a capacidade de realizar exercícios, as lesões (radiografia de tórax e TC) e a qualidade de vida justificam o esforço de se considerar o que deve ser feito quando os pacientes completam seu tratamento. Até onde sabemos, nenhuma revisão avaliou esse tópico de forma abrangente. Nosso objetivo foi revisar as evidências disponíveis e obter algumas conclusões sobre o futuro papel da fase de "tratamento pós-tuberculose", que irá potencialmente impactar milhões de casos todos os anos. Realizou-se uma revisão não sistemática da literatura tendo como base uma pesquisa no PubMed usando palavras-chave específicas (várias combinações dos termos "tuberculose", "reabilitação", "tuberculose multirresistente", "doença pulmonar", "doença pulmonar obstrutiva", e "medidas de volume pulmonar"). As listas de referências dos artigos principais foram recuperadas para melhorar a sensibilidade da busca. Foram selecionados manuscritos escritos em inglês, espanhol e russo. As principais áreas de interesse foram sequelas de tuberculose após diagnóstico e tratamento; "pulmão destruído"; avaliação funcional das sequelas; intervenções de reabilitação pulmonar (fisioterapia, oxigenoterapia de longo prazo e ventilação); e tuberculose multirresistente. As evidências encontradas sugerem que a tuberculose é definitivamente responsável por sequelas funcionais, principalmente causando um padrão obstrutivo na espirometria (mas também padrões restritivos e mistos) e que há razão para a reabilitação pulmonar. Fornecemos também uma lista de variáveis a serem discutidas em futuros estudos sobre reabilitação pulmonar em pacientes com sequelas pós-tuberculose.

ABSTRACT The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae.

Respiratory virus epidemics had highlighted the importance of the Intensive Care Unit (ICU) to save life of severe cases. ICU functioning and outcomes depends on infrastructure and trained healthcare personnel. In Chiapas, a Southern state in Mexico,an area to care for severe H1N1 cases on respiratory distress during the second H1N1-2009 outbreak, had to be habilitated.This had to be done without sufficient equipment and ICU un-experienced healthcare workers. It was possible to improve its performance through training and standardizing attention care processes for critically ill patients. In preparation for the next pandemic it is essential to designate hospitals with preexistent ICU where to refer severe cases and avoid improvisations.The experience in Chiapas showed that standardization of medical care processes are clue and in case of an overwhelming emergency it is possible to habilitate an ICU although it is imperative to take advantage from installed facilities in each city with the official authority.

Las epidemias de virus respiratorios en la era moderna han destacado la importancia de las unidades de terapia intensiva (UTI) para salvar la vida de pacientes graves. El desempeño de la UTI depende mucho del equipamiento y del personal capacitado. En Chiapas, durante el segundo brote de influenza H1N1-2009, se habilitó un área para atender enfermos graves con insuficiente equipamiento y con personal sin experiencia en UTI. Se logró mejorar su desempeño con una capacitación para estandarizar los procesos de atención del paciente en estado crítico.En la preparación para una próxima pandemia es esencial identificar anticipadamente los hospitales con UTI donde referir los casos graves y evitar improvisaciones. La experiencia en Chiapas demuestra que la estandarización de los procesos de atención es clave,y que en caso de una emergencia avasalladora es posible habilitar unidades sin dejar de lado la importancia de aprovechar la infraestructura instalada de cada ciudad con una decisión de autoridad.

Respiratory virus epidemics had highlighted the importance of the Intensive Care Unit (ICU) to save life of severe cases. ICU functioning and outcomes depends on infrastructure and trained healthcare personnel. In Chiapas, a Southern state in Mexico,an area to care for severe H1N1 cases on respiratory distress during the second H1N1-2009 outbreak, had to be habilitated.This had to be done without sufficient equipment and ICU un-experienced healthcare workers. It was possible to improve its performance through training and standardizing attention care processes for critically ill patients. In preparation for the next pandemic it is essential to designate hospitals with preexistent ICU where to refer severe cases and avoid improvisations.The experience in Chiapas showed that standardization of medical care processes are clue and in case of an overwhelming emergency it is possible to habilitate an ICU although it is imperative to take advantage from installed facilities in each city with the official authority.

Las epidemias de virus respiratorios en la era moderna han destacado la importancia de las unidades de terapia intensiva (UTI) para salvar la vida de pacientes graves. El desempeño de la UTI depende mucho del equipamiento y del personal capacitado. En Chiapas, durante el segundo brote de influenza H1N1-2009, se habilitó un área para atender enfermos graves con insuficiente equipamiento y con personal sin experiencia en UTI. Se logró mejorar su desempeño con una capacitación para estandarizar los procesos de atención del paciente en estado crítico.En la preparación para una próxima pandemia es esencial identificar anticipadamente los hospitales con UTI donde referir los casos graves y evitar improvisaciones. La experiencia en Chiapas demuestra que la estandarización de los procesos de atención es clave,y que en caso de una emergencia avasalladora es posible habilitar unidades sin dejar de lado la importancia de aprovechar la infraestructura instalada de cada ciudad con una decisión de autoridad.