Isolation of and risk factors for airway infection with Pseudomonas aeruginosa in patients with non-cystic fibrosis bronchiectasis / Isolamento de Pseudomonas aeruginosa e fatores de risco de infecção das vias aéreas pela bactéria em pacientes com bronquiectasias não fibrocísticas

ABSTRACT Objective: To identify microorganisms in sputum samples of patients with stable non-cystic fibrosis bronchiectasis and to determine risk factors related to the isolation of Pseudomonas aeruginosa (PA) in those patients. Methods: Consecutive patients were recruited from a tertiary hospital outpatient clinic in the city of Fortaleza, Brazil. The patients were submitted to spirometry, six-minute walk test, HRCT, and sputum collection. Data on serum fibrinogen levels, disease severity, sputum color, and history of azithromycin treatment were collected. Results: The study included 112 patients, and females predominated (68%). The mean age was 51.6 ± 17.4 years. Most patients presented with mild-to-moderate disease (83%). The mean six-minute walk distance was 468.8 ± 87.9 m. Mean FEV1 and FVC, in % of predicted values, were 60.4 ± 21.8% and 69.9 ± 18.5%, respectively. The mean serum fibrinogen level was 396.1 ± 76.3 mg/dL. PA was isolated in 47 patients, other potentially pathogenic microorganisms (PPMs) were isolated in 31 patients, and non-PPMs were isolated in 34 patients. Purulent sputum was identified in 77 patients (68%). The patients with PA, when compared with those without it, presented with more severe disease, higher serum fibrinogen levels, and lower FVC%. In addition, purulent sputum and long-term azithromycin treatment were more common in those with PA. The multivariate regression analysis showed that the independent factors associated with PA were serum fibrinogen level > 400 mg/dL (OR = 3.0; 95% CI: 1.1-7.7) and purulent sputum (OR = 4.3; 95% CI: 1.6-11.3). Conclusions: In our sample, the prevalence of PA in sputum was 42%. Sputum color and inflammatory markers were able to predict the isolation of PA, emphasizing the importance of routine sputum monitoring.

RESUMO Objetivo: Identificar microrganismos em amostras de escarro de pacientes com bronquiectasia não fibrocística estável e determinar os fatores de risco relacionados com o isolamento de Pseudomonas aeruginosa (PA) nesses pacientes. Métodos: Pacientes consecutivos foram recrutados em um ambulatório de um hospital terciário em Fortaleza (CE). Os pacientes foram submetidos a espirometria, teste de caminhada de seis minutos, TCAR e coleta de escarro. Foram coletados dados referentes ao fibrinogênio sérico, gravidade da doença, cor do escarro e histórico de tratamento com azitromicina. Resultados: O estudo incluiu 112 pacientes, com predomínio do sexo feminino (68%). A média de idade foi de 51,6 ± 17,4 anos. A maioria dos pacientes apresentou doença leve a moderada (83%). A média da distância percorrida no teste de caminhada de seis minutos foi de 468,8 ± 87,9 m. A média do VEF1 em % do previsto foi de 60,4 ± 21,8%, e a da CVF em % do previsto foi de 69,9 ± 18,5%. A média do fibrinogênio sérico foi de 396,1 ± 76,3 mg/dL. PA foi isolada em 47 pacientes; outros microrganismos potencialmente patogênicos (MPP) foram isolados em 31; não MPP foram isolados em 34. Escarro purulento foi identificado em 77 pacientes (68%). Os pacientes com PA, em comparação com aqueles sem, apresentaram doença mais grave, fibrinogênio sérico mais elevado e menor CVF%. Além disso, escarro purulento e tratamento prolongado com azitromicina foram mais comuns naqueles com PA. A análise de regressão multivariada mostrou que os fatores independentes relacionados com PA foram fibrinogênio sérico > 400 mg/dL (OR = 3,0; IC95%: 1,1-7,7) e escarro purulento (OR = 4,3; IC95%: 1,6-11,3). Conclusões: Em nossa amostra, a prevalência de PA no escarro foi de 42%. A cor do escarro e os marcadores inflamatórios foram capazes de prever o isolamento de PA, o que enfatiza a importância do monitoramento rotineiro do escarro.

Genotipificación de aislamientos del complejo Mycobacterium tuberculosis mediante MIRU-VNTR, Cali, Colombia, 2013-2015 / MIRU-VNTR genotyping of Mycobacterium tuberculosis in a population of patients in Cali, Colombia, 2013-2015

Resumen Introducción. La tuberculosis continúa siendo uno de los problemas de salud más importantes a nivel mundial y, con la infección por el virus de la inmunodeficiencia humana (HIV), constituye la principal causa de muerte por infecciones. En el 2016, se notificaron 6,3 millones de casos nuevos de la enfermedad. Objetivo. Describir los patrones genéticos determinados mediante la genotipificación del número variable de repeticiones en tándem de unidades repetitivas interespaciadas de micobacterias (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats, MIRU-VNTR) en la población de estudio y compararlos con los hallados en otros estudios locales e internacionales. Materiales y métodos. Mediante MIRU-VNTR, entre el 2013 y el 2015 se hizo la genotipificación de 105 muestras de ADN extraídas del esputo o de aislamientos en cultivo de M. tuberculosis provenientes de pacientes residentes en Cali con diagnóstico de tuberculosis pulmonar. La amplificación de 24 loci MIRU-VNTR se hizo por medio de la reacción en cadena de la polimerasa (PCR). Los amplicones resultantes se visualizaron por electroforesis en geles de agarosa (2 %) teñidos con SYBR Safe™. La asignación de los alelos se hizo con un análisis gráfico con el programa GelAnalyzer 2010. Los resultados obtenidos se analizaron con el algoritmo UPGMA y se compararon con las bases de datos internacionales MIRU-VNTRplus y SITVITWEB. Resultados. Se genotipificaron por completo 62 de las muestras y se obtuvieron 58 perfiles diferentes de MIRU-VNTR. Al comparar con las bases de datos internacionales, su distribución por linajes fue la siguiente: 54,8 % para el LAM, 25,8 % para el Haarlem, 14,5 % para el S, 3,2 % para el Beijing y 1,6 % para el Cameroon. Los patrones MIRU-VNTR correspondieron a 20 tipos internacionales de MIRU (MIRU International Types, MIT) diferentes, y los más frecuentes fueron el MIT 190 y el MIT 110, con 22,6 y 6,5 %, respectivamente. Conclusión. Estos resultados confirmaron hallazgos previos sobre el predominio de los linajes LAM y Haarlem en la ciudad y la presencia de los MIT encontrados en otra ciudad de Colombia.

Abstract Introduction: Tuberculosis continues to be one of the main public health problems in the world. Together with the HIV infection, it is one of the main causes of death due to infections worldwide. In 2016, 6.3 million new cases of the disease were reported. Objective: To describe the genetic patterns determined by genotyping using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) in the study population and compare them with other studies carried out in Cali, Colombia, and the world. Materials and methods: We genotyped a total of 105 DNA samples extracted from sputum or culture isolates of the Mycobacterium tuberculosis complex, which were obtained from pulmonary tuberculosis diagnosed patients over the period 2013-2015, in Cali. We performed PCR amplification of 24 loci by MIRU-VNTR on the DNA extracted from the samples. The amplicons were visualized in agarose gel electrophoresis (2%) with SYBR Safe™ staining. Then, the alleles were designated by graphical analysis using the GelAnalyzer 2010 software. These results were analyzed using the UPGMA logarithm and compared with the registers from the MIRU-VNTR plus and SITVITWEB databases. Results: We genotyped 62 of the samples completely and we obtained 58 different MIRU-VNTR profiles. By comparing with the international databases, we determined the following distributions per lineage: LAM, 54.8%; Haarlem,25.8%; S, 14.5%; Beijing, 3.2%, and Cameroon, 1.6%. The MIRU-VNTR patterns corresponded to 17 different MITs; the most frequent were MIT 190 and MIT 110, with 22.6% and 6.5%, respectively. Conclusions: These results demonstrated previous observations about the predominance of the LAM and Haarlem lineages in the city, and the presence of the MITs found in another city of Colombia.

La importancia de investigar Mycobacterium bovis en muestras clínicas de procedencia humana / Importance of investigating Mycobacterium bovis in clinical samples of human origin

Resumen Introducción. La tuberculosis es una enfermedad infectocontagiosa que continúa siendo un problema mundial de salud pública. Es la principal causa de mortalidad en personas con HIV. Objetivo. Identificar la presencia de Mycobacterium bovis como agente etiológico de tuberculosis humana en muestras de esputo con baciloscopia positiva, mediante la prueba Genotype MTBC™. Materiales y métodos. Se llevó a cabo un estudio descriptivo de 88 muestras de esputo remitidas al Grupo de Micobacterias del Instituto Nacional de Salud entre enero y noviembre de 2015. Se hizo el análisis microbiológico convencional y se empleó la prueba molecular de Genotype MTBC™ para diferenciar las especies del complejo M. tuberculosis. Resultados. Sesenta y dos casos (70,5 %) correspondían a pacientes de sexo masculino; los grupos más afectados fueron el de 24 a 34 años, el de residentes en las cabeceras municipales, y el de afiliados al régimen subsidiado. En el 50 % (44) de las muestras con resultados en la prueba de identificación de la especie, se detectó el complejo M. tuberculosis. Conclusiones. La mayor carga de la enfermedad se registró en la población masculina y en edad productiva. La prueba de identificación para especies del complejo, solo demostró la presencia de M. tuberculosis. Sin embargo, con estos datos no es posible descartar M. bovis en humanos con tuberculosis en Colombia. La identificación diferencial de la especie debería implementarse de forma rutinaria en los casos de tuberculosis en los grupos de riesgo y en las zonas donde se conoce la circulación de esta micobacteria en bovinos.

Abstract Introduction: Tuberculosis is an infectious disease that still represents a major public health problem worldwide. It is one of the main causes of mortality in people with HIV. Objective: To identify the presence of M. bovis as an etiological agent of human tuberculosis in sputum smear positive samples using the test Genotype MTBC™. Materials and methods: We conducted a descriptive study, 88 sputum samples were submitted to the Grupo de Micobacterias of the Instituto Nacional de Salud between January and November, 2015. We used the conventional microbiological analysis and the molecular test Genotype MTBC™ to identify the M. tuberculosis complex species. Results: Sixty two (70.5%) were males; the most affected groups were those between 24 and 34 years old, those residing in the municipal seats and those affiliated to the subsidized health plans. In 50.0% (44) of the samples with a result in the species identification test, we detected M. tuberculosis. Conclusion: The highest burden of the disease was recorded among the male population in productive ages. The identification test for species of the complex showed all were M. tuberculosis. However, it is not possible to discard the presence of M. bovis in humans in Colombia. The differential identification of species should be done in risk groups and in areas where the circulation of this mycobacterium in cattle is known.

Therapeutic itinerary of people with tuberculosis in face with their health needs / Itinerario terapéutico de personas con tuberculosis ante sus necesidades de salud / Itinerário terapêutico de pessoas com tuberculose diante de suas necessidades de saúde

Abstract Objective: To describe the therapeutic itinerary of people with tuberculosis in face of their health needs. Method: Descriptive, qualitative study. Semi-structured interviews were carried out with ten patients. Hermeneutic-dialectic method of analysis and concept of therapeutic itinerary as driver of the analysis. Results: Most had classic symptoms at the beginning, however there was a case with coughing for more than one year. Entrance door, access to diagnosis and treatment were predominant in Primary Care, through smear microscopy and X-ray; patients had to pay for exams. Decentralization of treatment for other services when necessary or by link with the professional. The patient followed the decisions of the professionals and the support of relatives; prejudice regarding the disease was noted. Conclusions and implications for practice: Fragility in disease management, importance of bonding and family. It should be considered the impact of the disease and the need to support patients to ensure continuity of care.

Resumen Objetivo: Describir el itinerario terapéutico de personas con tuberculosis ante sus necesidades de salud. Método: Estudio descriptivo, cualitativo. Se realizaron entrevistas semiestructuradas con diez pacientes. Método de análisis hermenéutico-dialéctico y concepto de itinerario terapéutico como conductor del análisis. Resultados: La mayoría presentó síntomas clásicos al inicio, pero hubo un caso con tos durante más de un año. Puerta de entrada, acceso al diagnóstico y tratamiento fueron predominantes en la Atención Primaria, a través de baciloscopía y radiografía; se realizó un seguimiento de los exámenes por los pacientes. Descentralización del tratamiento para otros servicios cuando necesario o por vínculo con el profesional. Paciente siguió las decisiones de los profesionales y del apoyo de familiares; prejuicio con la enfermedad. Conclusiones e implicaciones para la práctica: Fragilidad en el manejo de la enfermedad, importancia del vínculo y de la familia. Se debe considerar el impacto de la enfermedad y la necesidad de apoyo a los pacientes para garantizar la continuidad de la atención.

Resumo Objetivo: Descrever o itinerário terapêutico de pessoas com tuberculose diante de suas necessidades de saúde. Método: Estudo descritivo, qualitativo. Realizadas entrevistas semiestruturadas com dez pacientes. Método de análise hermenêutica-dialética e conceito de itinerário terapêutico como condutor da análise. Resultados: A maioria apresentou sintomas clássicos no início da doença, mas houve caso com tosse por mais de um ano. Porta de entrada, acesso ao diagnóstico e tratamento foram predominantes na Atenção Primária, através de baciloscopia e raio-X; houve custeio de exames pelos pacientes. Descentralização do tratamento para outros serviços quando necessário ou por vínculo com o profissional. O paciente seguiu as decisões dos profissionais e do apoio de familiares; constatou-se preconceito relativo à doença. Conclusões e implicações para a prática: Fragilidade no manejo da doença, importância do vínculo e da família. Deve-se considerar o impacto da doença e a necessidade de apoio aos pacientes para garantir a continuidade da atenção.

Biomass smoke COPD has less tomographic abnormalities but worse hypoxemia compared with tobacco COPD

Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients. However, the understanding of biomass smoke COPD is still limited and somewhat controversial. The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures. For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure. Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction. The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years. The tobacco COPD group smoked 48.5±27.4 pack-years. Women were 62.5 and 66.7%, respectively, of non-smokers and smokers. The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity. Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group. Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis. Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity.

Fatores associados à Doença Pulmonar Obstrutiva Crônica em idosos / Factors associated with Chronic Obstructive Pulmonary Disease among the elderly

Resumo Este estudo objetivou identificar os fatores associados à Doença Pulmonar Obstrutiva Crônica (DPOC) em idosos não institucionalizados. Trata-se de um estudo transversal conduzido a partir de inquérito domiciliar, seguido de espirometria. Pessoas com diagnóstico de DPOC foram comparadas com outras com espirometria normal, por meio de análises bivariadas seguidas de análise de regressão multivariada. Foram identificados 53 idosos com DPOC. Após análise multivariada, foram identificados os seguintes fatores associado à DPOC: tabagismo pregresso ou atual (OR:3,74; IC95%:1,65-8,46), presença de catarro como sintoma respiratório (OR:4,92; IC95%:2,03-11,95), oximetria de pulso em repouso ≤ 90% (OR:8,74; IC95%:1,27-60,07) e autorrelato de asma (OR:3,41; IC95%:1,01-11,57). Os resultados revelam fatores associados que destacam a necessidade de revisão dos critérios de seleção dos pacientes de risco para DPOC entre idosos.

Abstract This study aimed to identify factors associated with Chronic Obstructive Pulmonary Disease (COPD) among non-institutionalized elderly people. It involved a cross-sectional study conducted on the basis of a household survey, followed by spirometry. People diagnosed with COPD were compared with those with normal spirometry, through bivariate analysis, followed by multivariate regression analysis. We identified 53 elderly people were identified with COPD. After multivariate analysis, the following factors associated with COPD were identified: past or current smoking (OR: 3.74; 95% CI: 1.65-8.46), presence of chronic sputum (OR: 4.92; 95% CI: 2.03-11.95), pulse oximetry at rest ≤ 90% (OR: 8.74; 95%CI: 1.27-60.07), self-reported asthma (OR: 3.41; 95% CI: 1.01-11.57). The results reveal associated factors that highlight the need to review the selection criteria for patients at risk of COPD among the elderly.

Neumonía por Corynebacterium pseudodiphtheriticum / Pneumonia caused by Corynebacterium pseudodiphtheriticum

Corynebacterium pseudodiphtheriticum forma parte de la microbiota normal de orofaringe y de piel. Sin embargo, en las últimas décadas está emergiendo como oportunista causante de infecciones clínicamente significativas en pacientes con algún compromiso previo. Se refiere el caso clínico de una paciente de 76 años con antecedentes de hipertensión arterial, hipotiroidismo, diabetes tipo 2 e insuficiencia renal crónica, que presentó neumonía durante su estadía en terapia intensiva. El examen directo del esputo inducido (coloración de Gram) reveló una muestra representativa con abundante microbiota monomicrobiana constituida por bacilos gram positivos pleomórficos corineformes y el cultivo presencia de C. pseudodiphtheriticum. La paciente recibió medicación empírica con cefalosporina de tercera generación con evolución favorable.

Microorganisms of the genera Corynebacterium, specie pseudodiphtheriticum are a part of the indigenous microbiota of human skin and oropharinx. Nevertheless in recent decades these bacilli are emerging as opportunistic pathogens causing clinically significant infections in patients with previous compromise. We report the case of a 76 years old female patient, with a history of hypertension, hypothyroidism, type 2 diabetes and chronic renal failure, who presented pneumonia during their stay at the intensive care unit. The induced sputum revealed a representative sample with monomicrobial gram positive pleomorphic coryneform rods (Gram stain) and cultures demonstrated the presence of C. pseudodiphtheriticum as the only bacteria recovered. The pacient received an empirical third generation cephalosporin medication with a succesfull recovery.

Inflammatory and immunological profiles in patients with COPD: relationship with FEV 1 reversibility / Perfil inflamatório e imunológico em pacientes com DPOC: relação com a reversibilidade do VEF 1

ABSTRACT Objective: To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. Methods: This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Results: Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. Conclusions: COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile.

RESUMO Objetivo: Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. Métodos: Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. Resultados: Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. Conclusões: Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.

Heterogeneidad en los fenotipos inflamatorios de los pacientes con EPOC: rol del recuento celular diferencial en esputo / Heterogeneity of Inflammatory Phenotypes In Copd Patients: Role of Differential Cell Counting in Sputum

El tabaquismo es la principal causa de la EPOC, sin embargo, factores como la edad de diagnóstico, la historia previa de asma, exacerbaciones, predisposición genética y otros influirían en el desarrollo de la enfermedad. Esto estaría relacionado con los fenotipos de pacientes con EPOC, los cuales tendrían diferentes respuestas a los corticoides inhalados (CI). Recientemente, ha sido propuesto que los eosinófilos serían potenciales biomarcadores predictores de buena respuesta a los CI. Con la hipótesis de que la presencia de eosinófilos en esputo podría constituir una estrategia para diferenciar fenotipos de pacientes con EPOC, evaluamos los perfiles celulares infamatorios en muestras de esputo inducido en pacientes con EPOC no exacerbados. Para esto, se reclutaron 20 pacientes con EPOC moderado a severo que concurren al gimnasio de rehabilitación respiratoria, los cuales fueron agrupados en eosinofílicos (n: 8, cuando presentaron más de 3% de eosinófilos en la muestra de esputo inducido) o no eosinofílicos (n: 9). Se descartaron 3 muestras por contaminación con células epiteliales. Si bien no se observaron diferencias significativas en los test de función pulmonar o de marcha de 6 minutos, los pacientes con eosinoflia presentaron ligeramente mayor reversibilidad luego del broncodilatador. Además, tuvieron mayor eosinofilia periférica, mayores valores de FeNO y mejor calidad de vida (medida por cuestionarios) que los pacientes no eosinofílicos. El esputo inducido es una técnica no invasiva, económica, que representaría una herramienta útil para conocer los diferentes fenotipos inflamatorios en pacientes con EPOC.

Smoking is the major cause of COPD; however factors such as age, previous history of asthma, exacerbations, and genetic predisposition could infuence the development of the disease. This could be related with the phenotypes of COPD patients, who would have different responses to inhaled corticosteroids (ICs). Recently, it has been suggested that eosinophils are potential biomarkers that contribute to predict good response to ICs. To test the hypothesis that the presence of eosinophils in sputum could be useful to characterize different phenotypes of COPD patients, we assessed the infammatory cell profles in induced sputum samples from not exacerbated COPD patients. 20 patients with moderate to severe COPD, attending a pulmonary rehabilitation gym, were grouped into eosinophilic (8 patients who presented more than 3% eosinophils in the induced sputum sample) or neutrophilic (9 patients who had more than 60% neutrophils). Only 3 patients were excluded due to contamination of the sputum with epithelial cells. Although there were no-signifcant differences in the pulmonary function tests or the 6-minute walk, the patients with eosinophilia showed higher responsiveness to bronchodilator therapy. Besides this group presented an increase of peripheral eosinophils, higher FeNO and better quality of life (measured by questionnaires) compared with the neutrophilic patients. Induced sputum is an economic non-invasive technique and would be a useful tool to know different infammatory phenotypes in COPD patients.

Hiperinsuflação pulmonar com ventilador mecânico como manobra de higiene brônquica / Hyperinflation with mechanical ventilation as a bronchial hygiene maneuver

Introdução: Um dos objetivos da ventilação mecânica (VM) é a aplicação de terapêuticas específicas na higiene brônquica, como a hiperinsuflação mecânica com o ventilador, que visa promover a expansão das unidades atelectasiadas através dos canais colaterais, favorecendo o deslocamento da secreção pulmonar das vias aéreas periféricas para as centrais. Objetivos: Comparar a segurança e eficácia da técnica de hiperinsuflação com ventilador mecânico em relação à quantidade de secreção pulmonar aspirada com a técnica de aspiração isolada. Para isso, será realizada uma avaliação dos parâmetros ventilatórios e hemodinâmicos e da quantidade de secreção pulmonar aspirada antes e após as manobras e uma comparação entre os resultados obtidos por elas. Métodos: Ensaio clínico randomizado cruzado desenvolvido no centro de terapia intensiva (CTI) do Hospital de Clínicas de Porto Alegre. A amostra constituiu-se de 23 pacientes em VM. Resultados: Não foram encontradas diferenças significativas entre as manobras quanto à quantidade de secreção aspirada e aos valores hemodinâmicos e ventilatórios. A pressão arterial média (PAM) teve um aumento significativo após a manobra de aspiração, mas sem relevância clínica (AU)

Introduction: One of the objectives of mechanical ventilation (MV) is the application of specific therapies in bronchial hygiene, such as mechanical ventilator hyperinflation, which aims to promote the expansion of atelectatic units through the collateral channels, favoring the displacement of the pulmonary secretion from the peripheral airways to the central ones. Objectives: To compare the safety and efficacy of the mechanical ventilator hyperinflation technique in the amount of secretion aspirated with the technique of isolated aspiration. This was done by. evaluating the ventilatory and hemodynamic parameters and the amount of pulmonary secretion aspirated before and after the maneuvers and by comparing the results found in both of them. Methods: A randomized crossover clinical trial developed at the intensive care unit (ICU) of the Hospital de Clínicas de Porto Alegre. The sample consisted of 23 patients on MV. Results: There were no significant differences between the maneuvers regarding the amount of aspirated secretion and hemodynamic and ventilatory values. Mean arterial pressure (MAP) had a significant increase after the aspiration maneuver, but without clinical relevance. Conclusion: Hyperinflation with the mechanical ventilator is a safe technique and as effective as isolated aspiration as a bronchial hygiene technique (AU)

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Purulência do escarro e proteína C-reativa são preditores de mauprognóstico na exacerbação da doença pulmonar obstrutiva crônica / Sputum purulence and C-reactive protein are predictors of poor prognosis in exacerbation of chronic obstructive pulmonary disease

Entre os pacientes com exacerbação de doença pulmonar obstrutiva crônica (DPOC) de leve a moderada, aqueles com proteína C-reativa (PCR) em nível superior a 40 mg/L e aqueles com escarro purulento estão em maior risco de falha do tratamento sem antibióticos. Os pacientes sem essas características têm menos probabilidade de se beneficiarem de antibióticos e são candidatos a terapia sintomática com acompanhamento estrito.

Reliability of a rapid hematology stain for sputum cytology / Confiabilidade da coloração hematológica rápida para citologia de escarro

Objective: To determine the reliability of a rapid hematology stain for the cytological analysis of induced sputum samples. Methods: This was a cross-sectional study comparing the standard technique (May-Grünwald-Giemsa stain) with a rapid hematology stain (Diff-Quik). Of the 50 subjects included in the study, 21 had asthma, 19 had COPD, and 10 were healthy (controls). From the induced sputum samples collected, we prepared four slides: two were stained with May-Grünwald-Giemsa, and two were stained with Diff-Quik. The slides were read independently by two trained researchers blinded to the identification of the slides. The reliability for cell counting using the two techniques was evaluated by determining the intraclass correlation coefficients (ICCs) for intraobserver and interobserver agreement. Agreement in the identification of neutrophilic and eosinophilic sputum between the observers and between the stains was evaluated with kappa statistics. Results: In our comparison of the two staining techniques, the ICCs indicated almost perfect interobserver agreement for neutrophil, eosinophil, and macrophage counts (ICC: 0.98-1.00), as well as substantial agreement for lymphocyte counts (ICC: 0.76-0.83). Intraobserver agreement was almost perfect for neutrophil, eosinophil, and macrophage counts (ICC: 0.96-0.99), whereas it was moderate to substantial for lymphocyte counts (ICC = 0.65 and 0.75 for the two observers, respectively). Interobserver agreement for the identification of eosinophilic and neutrophilic sputum using the two techniques ranged from substantial to almost perfect (kappa range: 0.91-1.00). Conclusions: The use of Diff-Quik can be considered a reliable alternative for the processing of sputum samples. .

Objetivo: Determinar a confiabilidade da coloração hematológica rápida para a análise do escarro induzido. Métodos: Estudo transversal comparando a técnica padrão (coloração May-Grünwald-Giemsa) com a coloração hematológica rápida (panótico rápido). Participaram do estudo 50 indivíduos (21 asmáticos, 19 portadores de DPOC e 10 controles). Após a coleta do escarro induzido, foram preparadas 4 lâminas, sendo 2 coradas por May-Grünwald-Giemsa e 2 por panótico rápido. As lâminas foram lidas de forma independente por dois pesquisadores capacitados para o exame de escarro induzido e cegados para a identificação das lâminas. A confiabilidade para as contagens celulares dos dois métodos foi avaliada pela determinação dos coeficientes de correlação intraclasse (CCI) para as concordâncias intraobservador e interobservador. As concordâncias na identificação de escarro neutrofílico e eosinofílico entre observadores e entre as duas colorações foram calculadas por estatística kappa. Resultados: Nas duas colorações, os CCI apontaram concordância interobservador quase perfeita para as contagens de neutrófilos, eosinófilos e macrófagos (variação do CCI: 0,98-1,00) e substancial para as contagens de linfócitos (variação do CCI: 0,76-0,83). Na análise intraobservador, a concordância foi quase perfeita para as contagens de neutrófilos, eosinófilos e macrófagos (variação do CCI: 0,96-0,99) e de moderada a substancial para as contagens de linfócitos (CCI = 0,65 e 0,75 para observadores 1 e 2, respectivamente). A concordância interobservador na identificação de escarro eosinofílico e neutrofílico para os dois métodos de ...

Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

BACKGROUND: The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 µg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL). RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%). CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.

O programa de controle da tuberculose em Pelotas/RS, Brasil: investigação de contatos intradomiciliares / The tuberculosis control program in Pelotas/RS, Brazil: home contact investigations / El programa de control de la tuberculosis de Pelotas/RS, Brasil: investigación de contactos intradomiciliarios

Objetivou-se avaliar as ações de investigação dos contatos intradomiciliares dos casos índices de tuberculose (TB) no Programa de Controle da Tuberculose (PCT), de Pelotas/RS - Brasil. Trata-se de um estudo descritivo de corte transversal, com dados do prontuário dos casos índices. A amostra foi constituída por 163 contatos de 68 indivíduos com TB pulmonar em tratamento no PCT, entre junho e agosto de 2009. Os contatos eram, predominantemente, do sexo feminino, com idade acima dos 10 anos e filhos dos casos índices. Os exames solicitados foram a radiografia de tórax e a baciloscopia. Verificou-se a presença da doença ativa em 1,8% dos contatos. Os resultados evidenciam que a atenção à TB, em Pelotas/RS - Brasil, centralizada em um único serviço especializado, dificulta a investigação dos contatos intradomiciliares, necessitando envolver a atenção primária, para aproximar os profissionais da família e facilitar o diagnóstico precoce e a interrupção da cadeia de transmissão da TB em tempo oportuno.

The aim of this study is to evaluate the investigation actions of home contacts of tuberculosis (TB) index cases in the Tuberculosis Control Program (TCP) of Pelotas/RS - Brazil. This cross-sectional descriptive study was based on data from the records of index cases. The sample consisted of 163 contacts of 68 subjects with pulmonary TB in treatment in the TCP between June and August, 2009. These contacts were predominantly female, over 10 years of age and the daughters of index cases. The requested examination was a chest radiography and bacilloscopy. Active TB was found in 1.8 % of contacts. Results show that assistance for TB patients in Pelotas-Brazil, which is centralized in a single specialized service, hinders the investigation of home contacts. Primary care is required to narrow the gap between professionals and the family, and facilitate early diagnosis and interruption of the TB transmission chain in a timely manner.

El objetivo fue evaluar las acciones de investigación de los contactos intradomiciliaros de casos índices de tuberculosis (TB), en el Programa de Control de Tuberculosis (PCT) de Pelotas/RS - Brasil. Se trata de un estudio descriptivo de corte transversal, con datos del prontuario de los casos índices. La muestra fue constituida por 163 contactos de 68 sujetos con TB pulmonar en tratamiento en el PCT, entre julio y agosto de 2009. Los contactos eran predominantemente del sexo femenino, con edad superior a los 10 años e hijos del caso índice. Los exámenes solicitados fueron Rayos X del tórax y baciloscopia. Se verificó la presencia de la enfermedad activa en un 1,8% de los contactos. Los resultados evidencian que la atención a TB en Pelotas-Brasil, centralizada en un único servicio especializado, dificulta la investigación de los contactos intradomiciliarios, necesitando abarcar la atención primaria, para aproximar a los profesionales de la familia y facilitar el diagnóstico precoz y la interrupción de la cadena de transmisión de la TB en tiempo oportuno.

Consenso Intersociedades para el manejo de infecciones respiratorias: bronquitis aguda y enfermedad pulmonar obstructiva crónica / [Inter-society consensus for the management of respiratory infections: acute bronchitis and chronic obstructive pulmonary disease].

The Argentine Society for Infectious Diseases and other national societies issued updated practical guidelines for the management of acute bronchitis (AB) and reactivations of chronic obstructive pulmonary disease (COPD) with the aim of promoting rational use of diagnostic and therapeutic resources. AB is a condition characterized by inflammation of the bronchial airways which affects adults and children without underlying pulmonary disease. It is usually caused by a virus. The diagnosis is based on clinical findings after community acquired pneumonia has been ruled out. Treatment of AB is mainly symptomatic. Antibiotics should be used in immune-compromised hosts, patients with chronic respiratory or cardiac diseases and in the elderly with co-morbidities. Reactivation of COPD is defined as an acute change in the patient's baseline clinical situation beyond normal day to day variations, with an increase in dyspnea, sputum production and/or sputum purulence, warranting a change in medication. An increase in one symptom is considered a mild exacerbation, two as moderate, and the presence of three symptoms is considered a severe exacerbation. An infectious agent can be isolated in sputum in 50 to 75

of COPD reactivations. Moderate and severe episodes must be treated with antibiotics, amoxicillin/ beta-lactamase inhibitor, macrolides and fluoroquinolones are first choice drugs.

Valor del estudio celular del esputo en el seguimiento de las enfermedades inflamatorias de la vía aérea / Value of sputum analysis in the management of inflammatory airway diseases

El análisis celular del esputo, espontáneo u obtenido mediante la técnica de esputo inducido, se ha transformado en una herramienta ampliamente difundida para la evaluación y orientación del tratamiento de las enfermedades inflamatorias de la vía aérea, principalmente asma, enfermedad pulmonar obstructiva crónica y bronquitis eosinofílica. Se han aportado evidencias sobre la utilidad de la técnica del esputo inducido, validada y estandarizada, para ser empleada en pacientes con dificultades para expectorar. Numerosas investigaciones dieron cuenta de la efectividad de basar las decisiones terapéuticas en el componente inflamatorio de la vía aérea mediante el recuento de células en el esputo. Varios estudios mostraron que, en pacientes con asma el análisis celular de esputo guía en la determinación de estrategias para disminuir las exacerbaciones y para mejorar la función pulmonar, aun en pacientes con asma grave, para disminuir el remodelamiento; también se ha descrito su utilidad en pacientes con EPOC, para la disminución de las exacerbaciones.

Cellular analysis of sputum either spontaneous or by induced sputum technique, has become a widespread tool for the evaluation and guidance of treatment of inflammatory diseases of the airway, primarily asthma, COPD and eosinophilic bronchitis. Induced sputum method is a validated, standardized and non-invasive technique, useful in patients with difficulties to expectorate. Its implementation is simple and cost effective. Numerous investigations have shown the effectiveness of basing treatment decisions on the inflammatory component of the airway by counting cells in sputum. Several studies have demonstrated that in patients with asthma, results of this analysis can guide in defining strategies to reduce exacerbations and to improve lung function even in patients with severe asthma, as well as to decrease the remodeling; in addition, a reduction in exacerbations in COPD patients, monitored by this sputum examination, has also been described.

Tuberculosis and latent tuberculosis in prison inmates / Tuberculose e tuberculose latente na população prisional / Tuberculosis y tuberculosis latente en la población carcelaria

OBJECTIVE: To estimate the prevalences of tuberculosis and latent tuberculosis in inmates. METHODS: Observational study was carried out with inmates of a prison and a jail in the State of São Paulo, Southeastern Brazil, between March and December of 2008. Questionnaires were used to collect sociodemographic and epidemiological data. Tuberculin skin testing was administered (PPD-RT23-2TU/0.1 mL), and the following laboratory tests were also performed: sputum smear examination, sputum culture, identification of strains isolated and drug susceptibility testing. The variables were compared using Pearson's chi-square (Χ2) association test, Fisher's exact test and the proportion test. RESULTS: Of the 2,435 inmates interviewed, 2,237 (91.9 percent) agreed to submit to tuberculin skin testing and of these, 73.0 percent had positive reactions. The prevalence of tuberculosis was 830.6 per 100,000 inmates. The coefficients of prevalence were 1,029.5/100,000 for inmates of the prison and 525.7/100,000 for inmates of the jail. The sociodemographic characteristics of the inmates in the two groups studied were similar; most of the inmates were young and single with little schooling. The epidemiological characteristics differed between the prison units, with the number of cases of previous tuberculosis and of previous contact with the disease greater in the prison and coughing, expectoration and smoking more common in the jail. Among the 20 Mycobacterium tuberculosis strains identified, 95.0 percent were sensitive to anti-tuberculosis drugs, and 5.0 percent were resistant to streptomycin. CONCLUSIONS: The prevalences of tuberculosis and latent tuberculosis were higher in the incarcerated population than in the general population, and they were also higher in the prison than in the jail.

OBJETIVO: Estimar a prevalência da tuberculose e tuberculose latente em detentos. MÉTODOS: Estudo observacional foi realizado com detentos de uma penitenciária e de um centro de detenção provisória do Estado de São Paulo, SP, entre março e dezembro de 2008. Questionários foram utilizados para a coleta de dados sociodemográficos e epidemiológicos. O teste tuberculínico foi aplicado (PPD-RT23-2UT/0,1ml) e os seguintes exames laboratoriais foram realizados: baciloscopia de escarro, cultura de escarro, identificação das cepas isoladas e teste de sensibilidade às drogas antituberculose. As variáveis foram comparadas utilizando-se o teste de associação qui-quadrado de Person (Χ2), teste exato de Fisher e teste das proporções. RESULTADOS: Dos 2.435 detentos entrevistados, 2.237 (91,9 por cento) concordaram em submeter-se ao teste tuberculínico e destes, 73,0 por cento foram reatores. O coeficiente de prevalência da tuberculose foi de 830,6 por 100.000 detentos. Os coeficientes de prevalência foram de 1.029,5/100.000 detentos na penitenciária e de 525,7/100.000 detentos no centro de detenção provisória. As características sociodemográficas dos detentos nos dois grupos estudados foram semelhantes; a maioria dos detentos era jovem e solteiro com baixa escolaridade. As características epidemiológicas diferiram entre as unidades prisionais com o número de casos de tuberculose no passado e de contato prévio com doente maior na penitenciária e tosse, expectoração e hábito de fumar mais comum no centro de detenção. Entre as 20 cepas de Mycobacterium tuberculosis identificadas, 95,0 por cento foram sensíveis às drogas antituberculose e 5,0 por cento foram resistentes à estreptomicina. CONCLUSÕES: As prevalências da tuberculose e da tuberculose latente foram maiores na população carcerária do que na população geral; e também maiores na penitenciária do que no centro de detenção provisória.

OBJETIVO: Estimar la prevalencia de la tuberculosis y tuberculosis latente en detenidos. MÉTODOS: Estudio observacional realizado de marzo a diciembre de 200 con 4.435 detenidos de una penitenciaria y de un centro de detención provisional del Estado de Sao Paulo, sureste de Brasil, entre marzo y diciembre 2008. Cuestionarios fueron utilizados para colecta de datos sociodemográficos y epidemiológicos. Prueba tuberculina fue aplicada (PPD-RT23-2UT/0,1ml), así como los exámenes de laboratorio: baciloscopia de esputo, cultivo de esputo, identificación y prueba de sensibilidad a las drogas antituberculosis. Las variables fueron comparadas utilizándose la prueba de chi-cuadrado de Pearson, prueba exacta de Fisher y la prueba de las proporciones. RESULTADOS: De los 2.435 detenidos entrevistados, 2.237 (91,9 por ciento) concordaron a se someter a la prueba tuberculina y de estos, 73,0 por ciento reaccionaron. El coeficiente de incidencia de la tuberculosis fue de 830,6 por 100.000 detenidos. Los coeficientes de incidencia fueron de 1.029,5/100.000 detenidos en la penitenciaria y de 525,7/100.000 detenidos en el centro de detención provisional. Las características sociodemográficas de los detenidos de los dos grupos estudiados fueron semejantes; la mayoría de los detenidos era joven y soltero con baja escolaridad. Las características epidemiológicas se diferenciaron entre las unidades prisonales, con mayor número de casos de tuberculosis en el pasado y de contacto previo con enfermo en la penitenciaria; y mayor número de tos, expectoración y hábito de fumar en el centro de detención. Entre las 20 cepas de Mycobacterium tuberculosis identificadas, 95,0 por ciento fueron sensibles a las drogas antituberculosis y 5,0 por ciento fueron resistentes a la estreptomicina. CONCLUSIONES: Las prevalencias de la tuberculosis y de tuberculosis latente fueron mayores en la población carcelaria que en la población general; y mayores en la penitenciaria que en el centro de detención provisional.