Tuberculosis con resistencia a fármacos: nuevas definiciones de la OMS y su implicación en la Normativa de SEPAR / Drug Resistant Tuberculosis: New WHO Definitions and Their Implication in the SEPAR Guideline

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Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker.

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

In-Home Diagnosis of Obstructive Sleep Apnea Using Automatic Video Analysis / Diagnóstico domiciliario de apnea obstructiva del sueño utilizando el análisis automático de vídeo

Study objectives: To evaluate the diagnostic accuracy of a non-invasive technology based on image processing for the identification of obstructive sleep apnea (OSA) and its severity at patients' home. METHODS: Observational, prospective, diagnostic accuracy study to evaluate the degree of measure agreement between Sleepwise (SW), in-laboratory attended polysomnography (PSG) and a home sleep apnea test (HSAT). 38 consecutive subjects with suspected OSA referred as outpatients to the sleep unit were recruited from September 2016 to September 2017. All patients underwent in-laboratory attended PSG and image processing with SW simultaneously overnight. Subsequently, a HSAT and image processing with SW were performed simultaneously overnight at patients' home, and the 2 nights after, patients underwent only image processing with SW consecutively. RESULTS: In-laboratory polysomnography and SW had a Lin's concordance correlation coefficient of 0.933 and a Kappa of 0.930. Between HSAT and SW the Lin's concordance correlation coefficient was 0.842 and a Kappa of 0.571. Agreement between two consecutive nights with SW recording showed a Lin's concordance correlation coefficient of 0.923 and a Kappa of 0. 837. CONCLUSIONS: SW was highly accurate for non-invasive and automatic diagnosis of OSA in outpatients compared to standard methods for OSA diagnosis either in-laboratory attended PSG or HSAT. SW proved to be a technique with repeatable and concordant results on different nights for the same patient. We conclude SW is a non-invasive, easy-to-use, portable, effective and highly accurate system for the in-home diagnosis of OSA

OBJETIVOS: Evaluar la precisión diagnóstica de una tecnología no invasiva basada en el procesamiento de imágenes para la identificación de la apnea obstructiva del sueño (AOS) y su gravedad en el domicilio de los pacientes. MÉTODOS: Estudio observacional, prospectivo y de precisión diagnóstica para evaluar el grado de concordancia entre las mediciones de Sleepwise (SW), polisomnografía (PSG) asistida en el laboratorio y poligrafía respiratoria domiciliaria (PRD). Se reclutaron 38 sujetos consecutivos con sospecha de AOS, referidos como pacientes ambulatorios a la unidad de sueño entre septiembre de 2016 y septiembre de 2017. Se les realizó a todos una PSG y procesamiento de imagen con SW durante la noche en el laboratorio. Posteriormente, se realizó una PRD y procesamiento de imágenes con SW de forma simultánea durante la noche en su domicilio, y las 2 noches siguientes los pacientes se sometieron solo a procesamiento de imágenes con SW. RESULTADOS: La polisomnografía en el laboratorio y el SW mostraron un coeficiente de correlación de concordancia de Lin de 0,933 y un Kappa de 0,930. Entre la PRD y el SW el coeficiente de correlación de concordancia de Lin fue de 0,842 y un Kappa de 0,571. La concordancia entre las 2 noches consecutivas de grabación con el SW mostró un coeficiente de correlación de concordancia de Lin de 0,923 y un Kappa de 0,837. CONCLUSIONES: El SW mostró alta precisión para el diagnóstico no invasivo y automatizado de la AOS en pacientes ambulatorios en comparación con los métodos estándar para el diagnóstico de la AOS, ya sean la PSG asistida en el laboratorio o la PRD. El SW demostró ser una técnica con resultados reproducibles y concordantes en diferentes noches para el mismo paciente. Concluimos que la SW es un sistema no invasivo, fácil de usar, portátil, eficaz y altamente preciso para el diagnóstico domiciliario de la AOS

Evaluación del Programa Integrado de Investigación en Tuberculosis promovido por la sociedad española de Neumología y Cirugía Torácica tras 11 años de funcionamiento / Evaluation of the Integrated Tuberculosis Research Program Sponsored by the Spanish Society of Pulmonology and Thoracic Surgery: 11 Years on

OBJETIVO: El objetivo del estudio fue conocer la tendencia de las variables relacionadas con la tuberculosis (TB) en España a partir del registro del Programa Integrado de Investigación en Tuberculosis (PII-TB) de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) y evaluar el PII-TB mediante indicadores relacionados con sus objetivos científicos. MÉTODO: Estudio transversal multicéntrico de base poblacional de casos nuevos de TB registrados prospectivamente por el PII-TB entre 2006 y 2016. La tendencia temporal de variables cuantitativas se realizó mediante un modelo de regresión lineal y las cualitativas mediante la prueba de χ2 de tendencia lineal. RESULTADOS: Se analizaron 6.892 casos de TB con una mediana anual de 531. La tendencia general fue significativamente decreciente en mujeres, inmigrantes, privados de libertad y en tratados inicialmente con 3 fármacos. Se incrementaron significativamente la tendencia de grupos de 40 -50 años y > 50 años, primera atención por especialista de zona, hospitalización, retraso diagnóstico, localización diseminada y extrapulmonar única, cultivo (+), realización de antibiogramas, resistencia a fármacos, tratamiento directamente observado, prolongación del tratamiento y muerte por otra causa. Los objetivos científicos del PII-TB que incrementaron significativamente fueron las publicaciones alcanzando un máximo de 8 en 2016 y con un factor de impacto total de 49,664, y también mejoraron los proyectos iniciados anualmente, presentaciones en congresos y las tesis o tesinas. CONCLUSIONES: El PII-TB proporciona información relevante sobre la TB y sus factores asociados en España. Se ha formado un amplio equipo de investigadores y se han detectado aspectos científicos positivos y otros mejorables

OBJECTIVE: The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives. METHOD: Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend. RESULTS: A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant downward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40-50 and > 50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture (+), sensitivity testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49,664, numbers of projects initiated annually, presentations at conferences, and theses. CONCLUSIONS: PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved

Actualización de la normativa SEPAR «Diagnóstico y tratamiento de la tuberculosis con resistencia a fármacos» / Update of SEPAR guideline «Diagnosis and Treatment of Drug-Resistant Tuberculosis»

La evidencia acumulada en los 3 últimos años sobre el manejo clínico de la tuberculosis (TB) con resistencia a fármacos ha sido tan importante que hace necesario actualizar la normativa que SEPAR publicó en 2017, sobre todo en lo referente a nuevos métodos diagnósticos, a la clasificación racional de los fármacos con actividad frente a Mycobacterium tuberculosis y a los esquemas básicos a recomendar en los pacientes con TB con resistencia a isoniacida, con resistencia a rifampicina o con multifarmacorresistencia. En el diagnóstico de la enfermedad recomendamos la utilización de métodos moleculares rápidos que son útiles además para la detección precoz de mutaciones asociadas a resistencias a fármacos. Para el tratamiento de los enfermos con TB con multifarmacorresistencia se hace necesario dar prioridad a esquemas orales acortados que incluyan bedaquilina, una fluoroquinolona (levofloxacino o moxifloxacino) y linezolid en lugar de los esquemas cortos previamente recomendados con aminoglucósidos y otros muchos fármacos de menor eficacia y más tóxicos. La recomendación de la normativa es que el diseño de los tratamientos en estos pacientes, tanto el inicial como si se precisan cambios, sea consultado siempre con expertos en el manejo de TB con resistencia a fármacos y que se realicen por personal con experiencia en TB y en unidades que garanticen la supervisión de los tratamientos y el abordaje de sus reacciones adversas

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects

Diagnostic Accuracy of Interferon Gamma-Induced Protein 10 mRNA Release Assay for Tuberculosis.

Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.

Update of SEPAR guideline «Diagnosis and Treatment of Drug-Resistant Tuberculosis¼. / Actualización de la normativa SEPAR «Diagnóstico y tratamiento de la tuberculosis con resistencia a fármacos¼.

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects.

In-Home Diagnosis of Obstructive Sleep Apnea Using Automatic Video Analysis.

STUDY OBJECTIVES: To evaluate the diagnostic accuracy of a non-invasive technology based on image processing for the identification of obstructive sleep apnea (OSA) and its severity at patients' home. METHODS: Observational, prospective, diagnostic accuracy study to evaluate the degree of measure agreement between Sleepwise (SW), in-laboratory attended polysomnography (PSG) and a home sleep apnea test (HSAT). 38 consecutive subjects with suspected OSA referred as outpatients to the sleep unit were recruited from September 2016 to September 2017. All patients underwent in-laboratory attended PSG and image processing with SW simultaneously overnight. Subsequently, a HSAT and image processing with SW were performed simultaneously overnight at patients' home, and the 2 nights after, patients underwent only image processing with SW consecutively. RESULTS: In-laboratory polysomnography and SW had a Lin's concordance correlation coefficient of 0.933 and a κ of 0.930. Between HSAT and SW the Lin's concordance correlation coefficient was 0.842 and a κ of 0.571. Agreement between two consecutive nights with SW recording showed a Lin's concordance correlation coefficient of 0.923 and a κ of 0. 837. CONCLUSIONS: SW was highly accurate for non-invasive and automatic diagnosis of OSA in outpatients compared to standard methods for OSA diagnosis either in-laboratory attended PSG or HSAT. SW proved to be a technique with repeatable and concordant results on different nights for the same patient. We conclude SW is a non-invasive, easy-to-use, portable, effective and highly accurate system for the in-home diagnosis of OSA.

Evaluation of the Integrated Tuberculosis Research Program Sponsored by the Spanish Society of Pulmonology and Thoracic Surgery: 11 Years on. / Evaluación del Programa Integrado de Investigación en Tuberculosis promovido por la sociedad española de Neumología y Cirugía Torácica tras 11 años de funcionamiento.

OBJECTIVE: The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives. METHOD: Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend. RESULTS: A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant downward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40-50 and > 50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture(+), sensitivity testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49,664, numbers of projects initiated annually, presentations at conferences, and theses. CONCLUSIONS: PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved.

Asociación entre la contaminación ambiental y las agudizaciones de asma bronquial en Badalona (Barcelona), 2008-2016 / Association between air pollution and asthma exacerbations in Badalona, Barcelona (Spain), 2008-2016

Introducción y objetivo: La relación entre la contaminación ambiental y las enfermedades respiratorias ha sido ampliamente descrita, pero existen menos trabajos referentes a la contaminación y asma en nuestro medio. El objetivo del estudio fue analizar el efecto de la contaminación ambiental sobre las agudizaciones de asma. Material y métodos: Se trata de un estudio observacional. Se incluyeron en el análisis los ingresos hospitalarios diarios y las consultas a urgencias diarias en el Hospital Universitari Germans Trias i Pujol (Badalona, Barcelona) entre 2008 y 2016 de aquellos pacientes con diagnóstico de asma agudizada. Se obtuvieron los valores diarios de temperatura, humedad relativa, presión atmosférica y los niveles de NO2, SO2 y CO. Mediante regresión de Poisson simple se estudió la asociación entre estos factores y el número de hospitalizaciones y urgencias mediante regresiones simples para el mismo día y para entre uno y 4 días más tarde (lags 0 a 4). Se corrigió el efecto de las múltiples comparaciones. Resultados: Se asociaron con un incremento en las hospitalizaciones por asma la baja temperatura (lags 0 a 4) y los incrementos en los niveles de NO2 (lags 0, 1, 2 y 4) y presión atmosférica (lags 2 y 3). Al analizar las urgencias, estas se asociaron con la baja temperatura (lags 0, 1, 2, 3 y 4) y los incrementos en los niveles de NO2 (lags 2, 3 y 4). Conclusiones: La baja temperatura y la elevada concentración ambiental de NO2 se asocian con un incremento en las consultas a urgencias y hospitalizaciones por agudización de asma bronquial

Introduction and objective: Air pollution has been widely associated with respiratory diseases. Nevertheless, association between air pollution and exacerbations of asthma in our area has been less studied. To analyse the effect of air pollution on exacerbations of asthma in Badalona. Material and methods: This was an observational study conducted in Badalona. The number of daily hospital admissions and accident and emergency visits related to exacerbation of asthma between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, atmospheric pressure, relative humidity, and NO2, SO2 and CO levels on asthma-related emergencies and hospitalisations the same day and 1-4 days after. All p-values were corrected for multiple comparisons. Results: The number of hospitalisations was associated with low temperature (lags 0 to 4) and higher levels of NO2 (lags 0, 1, 2 and 4) and atmospheric pressure (lags 2 and 3). The number of accident and emergency visits was associated with low temperature (lags 0 to 4) and higher levels of NO2 (lags 2, 3 and 4). Conclusions: The number of accident and emergency visits and hospitalisations for exacerbation of asthma is associated with higher levels of NO2 and with lower temperatures

Association between air pollution and asthma exacerbations in Badalona, Barcelona (Spain), 2008-2016. / Asociación entre la contaminación ambiental y las agudizaciones de asma bronquial en Badalona (Barcelona), 2008-2016.

INTRODUCTION AND OBJECTIVE: Air pollution has been widely associated with respiratory diseases. Nevertheless, association between air pollution and exacerbations of asthma in our area has been less studied. To analyse the effect of air pollution on exacerbations of asthma in Badalona. MATERIAL AND METHODS: This was an observational study conducted in Badalona. The number of daily hospital admissions and accident and emergency visits related to exacerbation of asthma between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, atmospheric pressure, relative humidity, and NO2, SO2 and CO levels on asthma-related emergencies and hospitalisations the same day and 1-4 days after. All p-values were corrected for multiple comparisons. RESULTS: The number of hospitalisations was associated with low temperature (lags 0 to 4) and higher levels of NO2 (lags 0, 1, 2 and 4) and atmospheric pressure (lags 2 and 3). The number of accident and emergency visits was associated with low temperature (lags 0 to 4) and higher levels of NO2 (lags 2, 3 and 4). CONCLUSIONS: The number of accident and emergency visits and hospitalisations for exacerbation of asthma is associated with higher levels of NO2 and with lower temperatures.

Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.

INTRODUCTION: Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied. OBJECTIVE: To analyze the effect of air pollution on exacerbations of bronchiectasis. METHODS: This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1-4 days after. All p values were corrected for multiple comparisons. RESULTS: SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0-4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050). CONCLUSIONS: The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2.

Comentarios a la normativa SEPAR de diagnóstico y tratamiento de la tuberculosis con resistencia a fármacos / Comments on the SEPAR Guidelines for the Diagnosis and Treatment of Drug-Resistant Tuberculosis

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Systematic Compared With Targeted Staging With Endobronchial Ultrasound in Patients With Lung Cancer.

BACKGROUND: To evaluate the accuracy of systematic mediastinal staging by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) (sampling of all visible nodes measuring ≥5 mm from stations N3 to N1 regardless of their positron emission tomography/computed tomography [PET/CT] features) and compare this staging approach with targeted EBUS-TBNA staging (sampling only 18F-fluorodeoxyglucose [FDG]-avid nodes) in patients with N2 non-small cell lung cancer on PET/CT. METHODS: Retrospective study of 107 patients who underwent systematic EBUS-TBNA mediastinal staging. The results were compared with those of a hypothetical scenario where only FDG-avid nodes on PET/CT would be sampled. RESULTS: Systematic EBUS-TBNA sampling demonstrated N3 disease in 3 patients, N2 disease in 60 (42 single-station or N2a, 18 multiple-station or N2b) and N0/N1 disease in 44. Of these 44, 7 underwent mediastinoscopy, which did not show mediastinal disease; 6 of the 7 proceeded to lung resection, which also showed no mediastinal disease. Thirty-four N0/N1 patients after EBUS-TBNA underwent lung resection directly: N0/N1 was found in 30 and N2 in 4 (1 N2b with a PET/CT showing N2a disease, 3 N2a). Sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of systematic EBUS-TBNA were 94%, 100%, 90%, 100% and 96%, respectively. Compared with targeted EBUS-TBNA, systematic EBUS-TBNA sampling provided additional important clinical information in 14 cases (13%): 3 N3 cases would have passed unnoticed, and 11 N2b cases would have been staged as N2a. CONCLUSIONS: In clinical practice, systematic sampling of the mediastinum by EBUS-TBNA, regardless of PET/CT features, is to be recommended over targeted sampling.

Asociación entre factores ambientales e ingresos por bronquiectasias en Badalona, Barcelona (2007-2015) / Association between environmental factors and hospitalisations for bronchiectasis in Badalona, Barcelona, Spain (2007-2015)

Introducción: La relación entre los factores ambientales y las exacerbaciones de enfermedades respiratorias ha sido ampliamente estudiada. No obstante, no existen estudios que analicen la relación entre la contaminación ambiental y las agudizaciones por bronquiectasias. El objetivo de nuestro estudio es analizar la asociación entre la contaminación ambiental y los ingresos por bronquiectasias. Material y métodos: Se trata de un estudio observacional y retrospectivo, realizado en 2 hospitales de Badalona. Se obtuvo el número de ingresos hospitalarios por agudización de bronquiectasias entre los años 2007 y 2015. Mediante regresión binomial negativa se analizó la posible influencia de la temperatura ambiental y los valores mensuales medios de dióxido de azufre (SO2), óxido nítrico, dióxido de nitrógeno, ozono y monóxido de carbono en el número de ingresos mensuales por bronquiectasias. Todos los p-valores se corrigieron por comparaciones múltiples. Resultados: Todos los factores analizados, pero especialmente la temperatura, se asociaron de forma estadísticamente significativa con el número de ingresos por exacerbación de bronquiectasias. Al controlar el efecto de la temperatura en las variables de contaminación, solamente el SO2 mantuvo la significación estadística (p=0,008). Conclusión: El número de ingresos hospitalarios por agudización de bronquiectasias parece ser mayor en los meses con bajas temperaturas y/o altas concentraciones de SO2. Se necesitan estudios prospectivos con diferentes áreas geográficas que confirmen estos resultados

Introduction: The relationship between environmental factors and the exacerbation of respiratory diseases has been widely studied. However, there are no studies examining the relationship between these factors and bronchiectasis exacerbations. Our objective was to analyse the association between various environmental factors and hospitalisation for bronchiectasis. Material and methods: This was a retrospective observational study conducted at two hospitals in Badalona (Barcelona). The number of hospital admissions for exacerbation of bronchiectasis between 2007 and 2015 was obtained. Through multiple regression we analysed the relationship between the number of exacerbations and mean monthly values of temperature, SO2, NO, NO2, O3 and CO. Results: Temperature, SO2, NO, NO2, O3 and CO were significantly associated with an increase in admissions due to exacerbation of bronchiectasis. By controlling the effect of temperature on the pollution variables, only SO2 maintained statistical significance (P=.008). Conclusion: We have detected an increase in hospital admissions for exacerbation of bronchiectasis with increases in the atmospheric concentration of SO2 and the decrease in temperature. Prospective studies with different geographical locations to confirm these results are needed

Association between environmental factors and hospitalisations for bronchiectasis in Badalona, Barcelona, Spain (2007-2015). / Asociación entre factores ambientales e ingresos por bronquiectasias en Badalona, Barcelona (2007-2015).

INTRODUCTION: The relationship between environmental factors and the exacerbation of respiratory diseases has been widely studied. However, there are no studies examining the relationship between these factors and bronchiectasis exacerbations. Our objective was to analyse the association between various environmental factors and hospitalisation for bronchiectasis. MATERIAL AND METHODS: This was a retrospective observational study conducted at two hospitals in Badalona (Barcelona). The number of hospital admissions for exacerbation of bronchiectasis between 2007 and 2015 was obtained. Through multiple regression we analysed the relationship between the number of exacerbations and mean monthly values of temperature, SO2, NO, NO2, O3 and CO. RESULTS: Temperature, SO2, NO, NO2, O3 and CO were significantly associated with an increase in admissions due to exacerbation of bronchiectasis. By controlling the effect of temperature on the pollution variables, only SO2 maintained statistical significance (P=.008). CONCLUSION: We have detected an increase in hospital admissions for exacerbation of bronchiectasis with increases in the atmospheric concentration of SO2 and the decrease in temperature. Prospective studies with different geographical locations to confirm these results are needed.

Study of CD27 and CCR4 Markers on Specific CD4+ T-Cells as Immune Tools for Active and Latent Tuberculosis Management.

The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4+ T-cells producing IFN-γ+ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4+ T-cells producing: (i) IFN-γ+, (ii) TNF-α+, (iii) TNF-α+IFN-γ+, and (iv) IFN-γ+ and/or TNF-α+. The percentage of CD27- within all CD4+ T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4+ T-cells over MFI of CD27 in IFN-γ+CD4+ T-cells), being significantly increased during disease (p < 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4+ T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γ+TNF-α+CD4+ T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ+CD4+ T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ+TNF-α+CD4+ T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.

Effectiveness of treatment with nebulized colistin in patients with COPD.

OBJECTIVES: To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations. MATERIALS AND METHODS: Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included. Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after. RESULTS: After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre-post differences were detected in the number of exacerbations not requiring admission. CONCLUSION: Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results.