Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Caracterización clínica y tomográfica de pacientes hospitalizados con COVID-19 / Clinical and tomographic characterization of patients hospitalized with COVID-19

OBJETIVO: Realizar una caracterización clínica y por imágenes a pacientes hospitalizados por COVID-19 y analizar si existen predictores de riesgo asociados con una mayor gravedad. MÉTODO: Estudio observacional, retrospectivo. Se incluyeron pacientes hospitalizados con COVID-19, entre abril y julio de 2020. Se registraron datos demográficos, comorbilidades, exámenes de laboratorio, tipo de compromiso en tomografía computada (TC) de tórax, terapias recibidas y tipo de soporte respiratorio. En el análisis estadístico para identificar factores de riesgo se utilizó test χ2 de Pearson o test de Fisher para comparar variables categóricas y test de Mann-Whitney para comparar variables continuas. RESULTADOS: Se analizaron 164 pacientes. La mediana de edad fue de 57 años (rango 21 a 89). 111 pacientes (68%) de género masculino y mediana de 7 días de síntomas previo al ingreso (rango 1 a 23). 68 pacientes (41%) tienen obesidad (significativamente mayor en pacientes < 60 años, p = 0,026), 56 (34%) hipertensión arterial (HTA) y 43 (26%) diabetes. El patrón predominante en la TC de ingreso fue de vidrio esmerilado (VE) con "crazy paving" (35%) y luego VE puro (28%). Como indicador de gravedad se tomó en cuenta el tipo de soporte ventilatorio requerido: 51 pacientes (31%) requieren soporte ventilatorio no invasivo (cánula nasal de alto flujo o VMNI) y 19 (11%) ventilación invasiva (VMI). Las variables predictoras de gravedad, estadísticamente significativas, fueron: HTA (p = 0,001), Diabetes Mellitus (p = 0,001) y Obesidad. (p = 0,002). CONCLUSIONES: Los pacientes hospitalizados por COVID 19 con mayor riesgo de evolución tórpida, del punto de vista respiratorio, fueron los pacientes obesos, hipertensos y diabéticos.

OBJECTIVE: To perform a clinical and imaging characterization in patients hospitalized for COVID-19 and to analyze whether there are risk predictors associated with greater severity of the condition. METHOD: Observational, retrospective study. Patients hospitalized with COVID-19 were included between April and July 2020. Demographic data, comorbidities, laboratory tests, tomographic pattern in thorax tomography (TC), therapies received, and type of respiratory support were recorded. In the statistical analysis to identify risk factors, we used Pearson's χ2 test or Fisher's test to compare categorical variables and Mann-Whitney test to compare continuous variables. RESULTS: 164 patients were analyzed. Median age was 57 years (21 to 89). 111 patients (68%) were male and a median of 7 days of symptoms prior to admission (1 to 23). 68 patients (41%) have obesity (significantly higher in patients < 60 years, p = 0.026), 56 (34%) arterial hypertension (HT) and 43 (26%) with diabetes mellitus. The predominant pattern in the admission CT scan was ground glass opacity (GGO) with "crazy paving" (35%) and then pure GGO (28%). Type of ventilatory support required was considered as an indicator of severity. 51 patients (31%) require non-invasive ventilatory support (high-flow nasal cannula or NIMV) and 19 (11%) invasive ventilation (IMV). The statistically significant predictor variables of severity were HT (p = 0.001), Diabetes Mellitus (p = 0.001) and Obesity. (p = 0.002). CONCLUSIONS: Patients hospitalized for COVID 19 with the highest risk of respiratory torpid evolution were obese, hypertensive and diabetic patients

Trasplante pulmonar ex vivo: primera experiencia en Chile y Latinoamérica / Lung transplant with ex vivo lung perfusion, Chilean and Latin American first experience

Background: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. Aim: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. Material and Methods: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020. High risk donor lungs and rejected lungs from other transplantation centers were included. The "Toronto Protocol" was used for ex vivo lung perfusion. Donor lung characteristics and recipient outcomes were studied. Results: During the study period, five ex vivo lung perfusions were performed. All lungs were reconditioned and transplanted. No complications were associated. There were no primary graft dysfunctions and only one chronic allograft dysfunction. There was no mortality during the first year. The median arterial oxygen partial pressure/fractional inspired oxygen ratio increased from 266 mm Hg in the donor lung to 419 after 3 hours of ex vivo lung perfusion (p = 0.043). Conclusions: ex vivo lung perfusion is a safe and useful tool that allows marginal donor lungs to be reconditioned and successfully transplanted.

Ecuaciones de referencia para informe de espirometrías. ¿Será tiempo de adoptar las ecuaciones de la Global Initiative for Lung Function? / Reference equations for spirometry values. Should be time for adopting the Global Lung Function Initiative equations?

Las guías ATS/ERS recomiendan utilizar valores de referencia nacionales para la interpretación de la espirometría. En 2014 se publicaron valores de referencia en población general chilena adulta, que difieren de los de Knudson actualmente en uso. Sin embargo, la mayoría de los laboratorios de función pulmonar siguen utilizando estas últimas ecuaciones. En 2012 se publicaron las ecuaciones multi-étnicas de la Global Lung Function Initiative (GLI) a fin de estandarizar mundialmente la interpretación de los exámenes de función pulmonar Nuestro objetivo fue comparar la concordancia de los informes espirométricos utilizando las ecuaciones más usadas en Chile versus las GLI. Métodos: Se comparó la concordancia en interpretación del patrón espirométrico (normal, obstructivo y restrictivo) y el grado de alteración, entre GLI con Gutiérrez 2014, con Knudson, y con NHANES III según las recomendaciones de la Sociedad Chilena de Enfermedades Respiratorias, a través del coeficiente de concordancia Kappa (K). Se estudiaron 315 sujetos mayores de 40 años (55% mujeres, edad: 59,3 ± 9,2 años), fumadores o ex fumadores, sanos o con EPOC, sometidos a una espirometría con broncodilatador como parte de un reconocimiento respiratorio. Se graficaron las diferencias utilizando el método de Bland-Altman. Resultados: La concordancia para patrón entre GLI con Gutiérrez 2014, con Knudson y con NHANES III fue buena (K = 0,73; 0,71 y 0,77 respectivamente), al igual que para patrón y grado de alteración (K = 0,68; 0,67 y 0,76 respectivamente). Conclusiones: Encontramos una buena concordancia entre las ecuaciones más usadas en Chile y las de GLI, en una muestra que incluyó adultos, fumadores, ex fumadores sanos y enfermos.

ATS/ERS recommend the use of national reference values for the interpretation of spirometry. Reference values were published (2014) in general adult Chilean population, which are different from those of Knudson currently in use. However, most pulmonary function laboratories continue to use these latter equations. Multi-ethnic Global Lung Function Initiative (GLI) equations were published (2012) in order to standardize the interpretation of pulmonary function tests worldwide. Our objective was to evaluate the agreement in the spirometric reports between the most used equations in Chile with those from GLI. Methods: We compared the agreement in the interpretation of the spirometric pattern (normal, obstructive and restrictive) and the degree of alteration between GLI with Gutiérrez 2014, with Knudson and with NHANES III according to recommendations of the Chilean Society of Respiratory Diseases, through the Kappa concordance coefficient (K). The sample correspond to 315 adults over 40 years of age (55% women, 59.3 ± 9.2 years-old), smokers or ex-smokers, healthy or with COPD, who underwent spirometry with a bronchodilator as part of a respiratory check-up. Differences were plotted using the Bland-Altman method. Results: agreement for pattern between GLI with Gutiérrez 2014, with Knudson and with NHANES III was good (K = 0.73, 0.71 and 0.77 respectively) and also was good for the pattern and degree of alteration (K = 0.68, 0.67 and 0.76 respectively). Conclusions: We found a good agreement between the equations most used in Chile and those from the GLI, for a sample that includes subjects with and without lung disease, smokers and ex-smokers.

Características clínicas de los pacientes con apneas obstructivas del sueño: diferencias según género / Clinical features in patients with obstructive sleep apnea syndrome: differences by gender

INTRODUCCIÓN: El síndrome de apnea obstructiva del sueño (SAHOS) es más prevalente en hombres, los estudios poblacionales muestran una relación de 2:1, sin embargo, en los estudios clínicos la frecuencia llega a ser de hasta de 6:1. Estas diferencias en el ambiente clínico puede ser consecuencia de variaciones en el reporte de síntomas en hombres comparados con mujeres. OBJETIVO: Evaluar las diferencias de género en la presentación clínica de apnea obstructiva de sueño. Pacientes: Estudio transversal de pacientes sometidos a una poligrafía respiratoria (PR) con sospecha clínica de SAHOS. Se recolectaron datos demográficos, antropométricos, comorbilidades y las variables de la PR. Se realizó estudio t de student, Mann-Whitney y chi-cuadrado según correspondiera. RESULTADOS: Se incluyeron 1.044 pacientes: edad promedio 53,2 ± 14 años, 76% hombres. Las mujeres con SAHOS poseen mayor IMC (32,2 ± 6,1 vs 30,8 ± 5,0; p=0,002) y edad (61,4 ± 12,2 vs 52,6 ± 13,9; p < 0,001), pero menor circunferencia de cuello (CC) (38,1 ± 3,6 vs 43,2 ± 3,3; p < 0,001), además, presentan menor IA/H y menor duración de las apneas. No hubo diferencias en los síntomas clásicos de apneas presenciada y somnolencia diurna, sin embargo, describen más frecuentemente insomnio, cefalea matinal, depresión y uso de fármacos hipnóticos. CONCLUSIONES: Las mujeres al momento del diagnóstico son de mayor edad y más obesas, aunque presentan una CC menor, presentan una enfermedad más leve, pero refieren más fatiga, cansancio, cefalea e insomnio. Debemos estar alerta en la presentación clínica diferente de las mujeres para mejorar la sospecha diagnóstica.

INTRODUCTION: Obstructive sleep apnea (OSA) is more prevalent in men, population studies show a ratio of 2:1, however in clinical studies the frequency is as high as 6:1. These differences in the clinical setting may be a consequence of variations in the reporting of symptoms in men compared to women. OBJECTIVE: To evaluate gender differences between women and men with recent diagnosis of OSA. Patients: A cross-sectional, study of patients undergoing home sleep apnea testing (HSAT) with clinical suspicion of OSA. Demographic, anthropometric, comorbidities and HSAT variables were collected. We performed t student analysis, Mann-Whitney test or chi square test as appropriate. RESULTS: 1,044 patients were included: mean age 53.2 ± 14 years, 76% men. Women with OSA have a higher BMI (32.2 ± 6.1 vs 30.8 ± 5.0, p = 0.002), were older (61.4 ± 12.2 vs 52.6 ± 13.9, p <0.001), but have a lower neck circumference (NC) (38.1 ± 3.6 vs. 43.2 ± 3.3, p <0.001). The women presented lower AHI and shorter duration of apneas. Although the classic symptoms of apnea and daytime sleepiness showed no differences, women reported more frequently insomnia, morning headache, depression and use of hypnotic drugs. CONCLUSIONS:: Clinical differences between gender are present at time of diagnosis. Woman are older and more obese, although they have a lower NC. They have a milder disease, but they refer to be more tired, headache, insomnia and depression. We must be alert in the different clinical presentation of women to improve the diagnostic suspicion.

Diferencias clínicas en pacientes con apnea obstructiva del sueño de carácter postural / Clinical differences in positional obstructive sleep apnea patients

Introduction: Obstructive sleep apnea syndrome (OSA) is the result of repetitive collapse of the upper airway during the sleep. There is a group of patients with a positional component; which is defined as a reduction of at least 50% in the apnea hypopnea index (AHI) from the supine to a lateral position. Objective: The purpose of this study is to determine positional OSA prevalence and compare clinical characteristics and polygraph recordings among this group of patients. Methods: Prospective study of polygraph recording of patients with suspect of OSA between 2009-2014. Demographic, anthropometric, comorbidities and polygraph recording data was collected. OSA was defined as AHI > 5 events per hour Results: From a total of 457 patients with OSA diagnose, 243 had a positional component (53%). Positional Sleep Apnea patients had mild AHI (p < 0.001), a lower neck circumference (p = 0.001), lower Body Mass Index (p = 0.003) and a lower presence of arterial hypertension (p = 0.001). The multivariable analysis confirmed that there is a lower probability in Positional OSA in patients with Severe AHI (OR 0,96: IC 0,94-0,97), with hypertension (0,54: IC 0,33-0,88) and males (OR 0,41: IC 0,21-0,81). Conclusions: Positional obstructive sleep apnea is a very frequent condition presented in 53% of OSA patients; these patients have often mild AHI, lower BMI, lower neck circumference, less hypertensive, and are usually females.

Introducción: El síndrome de apnea e hipopnea obstructiva del sueño (SAHOS) es producto de un colapso repetido a nivel de la vía aérea superior, durante el sueño. Existe un grupo de pacientes con SAHOS con componente postural, definida por una reducción del 50% o más en el índice de apnea hipopnea (IAH) de la posición supina a la lateral. Objetivo: Determinar la prevalencia de SAHOS postural y comparar las características clínicas y de la poligrafía respiratoria (PR) de este grupo de pacientes. Metodología: Estudio prospectivo de PR entre 2009-2014, derivados a realización de estudio por sospecha clínica de SAHOS. Se recolectaron datos demográficos, antropométricos, comorbilidades y diferentes variables de la PR. Se definió presencia de SAHOS un IAH mayor de 5 eventos/h. Resultados: De un total de 457pacientes con diagnóstico de SAHOS, 243presentaban SAHOS postural (53%). Los pacientes con SAHOS postural eran más leves (p < 0,001), tenían una circunferencia cervical (p = 0,001) e índice de masa corporal (p = 0,003) menor y con menor frecuencia eran hipertensos (p = 0,001). El análisis multivariado confirmó menor probabilidad SAHOS postural en sujetos con IAH graves (OR 0,96: IC 0,94-0,97): hipertensos (0,54: IC 0,33-0,88) y de sexo masculino (OR 0,41: IC 0,21-0,81). Conclusiones: El SAHOS postural es una entidad muy frecuente que está presente en el 53% de los pacientes con SAHOS, estos sujetos tienden a presentar enfermedad más leve, tener un IMC y circunferencia cervical menor, menor frecuencia de hipertensión arterial y son preferentemente mujeres.

Hipertensión pulmonar en pacientes con fibrosis pulmonar y sobrevida post-trasplante pulmonar / Pulmonary hypertension in patients with pulmonary fibrosis and survival after lung transplant

Introduction: The presence ofpulmonary hypertension (PH) in patients with pulmonary fibrosis is a predictor of severity andpoor survival in patients awaiting lung transplantation. Little is known about the impact of PH on survival after lung transplantation. Objective: To evaluate the effect of PH in pulmonary fibrosis patient survival after lung transplantation. Methods: Retrospective study ofpatients diagnosed with pulmonary fibrosis subjected to lung transplantation at the Instituto Nacional del Tórax during the period of August 2010 to June 2015. Thresholds of > 25 and > 35 mm Hg were chosen for mean pulmonary artery pressure (PAmean) and systolic pulmonary artery pressure (PAsystolic), respectively as indicators of PH. Results: Out of a total of 63 patients undergoing lung transplantation during the 2010-2015 period, 42 patients were diagnosed with pulmonary fibrosis. 35 of these patients had histologic diagnosis of usual interstitial pneumonia (UIP) and 7 of extrinsic allergic alveolitis in fibrotic stage. Of the total 25 patients with pulmonary fibrosis (60 percent) had PH in the pre-transplant period. A total of 15 patients died during the follow-up. There was no significant difference in survival between patients with and without PH (p = 0.74). Conclusions: Similar to international studies, we observed that the presence of PH in patients with pulmonary fibrosis did not increase risk of death in post-transplant period.

Introducción: La presencia de hipertensión pulmonar (HTP) en pacientes con fibrosis pulmonar es un predictor de gravedad y pobre sobrevida en pacientes en espera de trasplante pulmonar. Poco se sabe del impacto de la HTP en la sobrevida de los pacientes en el período post trasplante. Objetivo: Evaluar el efecto de la HTP en la sobrevida de los pacientes con fibrosis pulmonar sometidos a trasplante pulmonar. Material y Método: Estudio retrospectivo de pacientes con diagnóstico de fibrosis pulmonar sometidos a trasplante pulmonar en el Instituto Nacional de Tórax durante el período de agosto de 2010 a junio de 2015. Los criterios diagnósticos de hipertensión pulmonar fueron: presión de arteria pulmonar media mayor o igual a 25 mmHg y/o presión sistólica de arteria pulmonar mayor o igual a 35 mmHg. Resultados: De un total de 63 pacientes sometidos a trasplante pulmonar durante el período 2010-2015 en el Hospital del Tórax, 42 pacientes tenían diagnóstico de fibrosis pulmonar. De estos, 35 pacientes tenían diagnóstico histológico de neumonía intersticial usual (UIP) y 7 de alveolitis alérgica extrínseca en etapa fibrótica. Del total de pacientes con fibrosis pulmonar, 25 (60 por ciento) presentaba HTP en el período pre trasplante. Un total de 15 pacientes fallecieron durante el seguimiento. Al comparar la sobrevida post trasplante de pacientes con HTP vs sin HTP no se observó diferencia significativa (p = 0,74). Conclusiones: Al igual que en estudios internacionales, no observamos que la presencia de HTP en pacientes con fibrosis pulmonar aumente el riesgo de muerte en el período post-trasplante.

Caracterización de las infecciones respiratorias en pacientes adultos oncológicos / Clinical characteristics of respiratory infections in patients with cancer

Introduction: Infections are common in oncology. Aim: To characterize respiratory infections in hospitalized adult cancer patients. Methods: Prospective, descriptive study of febrile adult patients in oncology at the Hospital Clínico Universidad Católica de Chile, between April 2008 and April 2009. Results: 187 episodes were evaluated. Clinical infection was recognized in 70% and 33 episodes (25%) were respiratory focus. Neoplastic disease corresponded to solid organ cancer in 77% of cases and 33% were admitted with febrile neutropenia. The upper respiratory tract infection accounted for 36% and low respiratory tract infection 65% of cases; 55% was pneumonia. Etiology of these was isolated in 39% (S. pneumoniae 2 cases, S. bovis 1, E. faecalis 1, P. jirovecii 2, S. maltophilia 1 and A. fumigatus 1). Hospital mortality for pneumonia was 22% and overall mortality 12%. Conclusions: Respiratory infections are a major focus in adult cancer patients, highlighting pneumonia. It carries high mortality and varied etiology.

Introducción: Las infecciones en oncología son frecuentes. Objetivo: Caracterizar las infecciones respiratorias en pacientes oncológicos hospitalizados. Métodos: Estudio descriptivo prospectivo de pacientes adultos oncológicos febriles en el Hospital Clínico de la Universidad Católica, entre abril de 2008 y abril de 2009. Resultados: Se evaluaron 187 episodios. Se identificó foco clínico en 70% y 33 episodios (25%) correspondieron a foco respiratorio. La patología oncológica correspondió a tumores de órgano sólido en 77% de los casos y el 33% ingresó con neutropenia febril. La infección respiratoria alta representó el 36% y baja un 65% de los casos; 55% fueron neumonía. De estos, se aisló el agente causal en un 39% (S. pneumoniae 2 casos, S. bovis 1, E. faecalis 1, P. jirovecii 2, S. maltophilia 1 y A. fumigatus 1). La letalidad en el hospital por neumonía fue 22% y la mortalidad general 12%. Conclusiones: La infección respiratoria es un motivo de consulta y hospitalización frecuente en pacientes oncológicos, destacando la neumonía. Conlleva elevada mortalidad y etiología variada.

Dificultades en la elección de una ecuación de referencia para la interpretación de los resultados de capacidad de difusión de monóxido de carbono / Difficulties in the selection of a reference equation for the interpretation of the results of DLCO

Introduction: In the absence of national reference equations, the ATS recommends comparing the results of the diffusion capacity of healthy subjects in a representative sample of the population with international equations and choosing among them, the one that provides the lowest sum of the residues. Objective: To compare reference equations available in the literature and identify which best meets the selection criteria. Methods: We reviewed 10 reference equations, for each one we calculated the sum of the residues for a sample of 71 healthy subjects and described the characteristics that affect the variability of each one. Results: Since 1985 we have used the single breath method. Only Thompson et al prediction equations 2008 were obtained with instantaneous reading of CO. Equations with the lowest sum of residues (Miller, Roca and Cotes) include smokers and former smokers. Conclusions: We need an equation in non-smokers with methodology that ensures low variability.

Introducción: En ausencia de ecuaciones de referencia nacionales, la ATS recomienda comparar los resultados de capacidad de difusión de monóxido de carbono de sujetos sanos en una muestra representativa de la población, con ecuaciones internacionales y escoger entre estas, aquella que presente la menor suma de los residuos. Objetivo: Comparar las ecuaciones de referencia disponibles en la literatura e identificar cuál cumple mejor los criterios de selección. Método: Revisamos 10 ecuaciones de referencia; calculamos la suma de los residuos de cada una de ellas para una muestra de 71 sujetos sanos y describimos las características que inciden en la variabilidad de cada una. Resultados: Desde 1985 se ha utilizado el método de respiración única. Sólo las ecuaciones de Thompson y cols. 2008fueron obtenidas con lectura instantánea. Las ecuaciones que presentan menor suma de residuos (Miller, Roca y Cotes) incluyen fumadores y ex fumadores. Conclusiones: Es necesaria una ecuación nacional en sujetos sanos no fumadores, con metodología que asegure baja variabilidad.

Etiología y biomarcadores de inflamación sistémica en las exacerbaciones leves a moderadas de la enfermedad pulmonar obstructiva crónica / Etiology and biomarkers of systemic inflammation in mild to moderate COPD exacerbations

Background: The etiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Inflammation increases during exacerbation of COPD. The identification of inflammatory changes will increase our knowledge and potentially guide therapy. Aim: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and viral exacerbations. Material and Methods: In 85 COPD patients (45 males, mean age 68 ± 8 years, FEV1 46 ± 17% of predicted) sputum, nasopharyngeal swabs and blood samples were collected to identify the causative organism, during a mild to moderate exacerbation. Serum ultrasensitive C reactive protein (CRP), fibrinogen and interleukin 6 (IL 6), neutrophil and leukocyte counts were measured in stable conditions, during a COPD exacerbation, 15 and 30 days post exacerbation. Results: A total of 120 mild to moderate COPD exacerbations were included. In 74 (61.7%), a microbial etiology could be identified, most commonly Mycoplasma pneumoniae (15.8%), Rhinovirus (15%), Haemophilus influenzae (14.2%), Chlamydia pneumoniae (11.7%), Streptococcus pneumoniae (5.8%) and Gram negative bacilli (5.8%). Serum CRP, fibrinogen and IL 6, and neutrophil and leukocyte counts significantly increased during exacerbation and recovered at 30 days post exacerbation. Compared to viral exacerbations, bacterial aggravations were associated with a systemic inflammation of higher magnitude. Conclusions: Biomarkers of systemic inflammation increase during mild to moderate COPD exacerbations. The increase in systemic inflammation seems to be limited to exacerbations caused by bacterial infections.

Prueba de caminata en seis minutos en sujetos chilenos sanos de 20 a 80 años / Reference values for the 6-minutes walking test in healthy subjects 20-80 years old

Background: The six minute walking distance test (6MWD) is widely used to evaluate exercise capacity in several diseases due to its simplicity and low cost. Aim: To establish reference values for 6MWD in healthy Chilean individuals. Material and methods: We studied 175 healthy volunteers aged 20-80 years (98 women) with normal spirometry and without history of respiratory, cardiovascular or other diseases that could impair walking capacity. The test was performed twice with an interval of 30 min. Heart rate, arterial oxygen saturation (with a pulse oxymeter) and dyspnea were measured before and after the test. Results: Walking distance was 576 ± 87 m in women and 644 ± 84 m in men (p < 0.0001). For each sex, a model including age, height and weight produced 6MWD prediction equations with a coefficient of determination (R²) of 0.63 for women and 0.55 for men. Conclusions: Our results provide reference equations for 6MWD that are valid for healthy subjects between 20 and 80 years old.

Marcadores de inflamación sistémica en pacientes ex fumadores con enfermedad pulmonar obstructiva crónica en etapa estable / Systemic inflammation among stable ex smokers with chronic obstructive pulmonary disease

Background: Low grade systemic inflammation is commonly observed in chronic obstructive pulmonary disease (COPD). Aim: To evaluate the extent of systemic inflammation in a group of ex-smokers with COPD in stable condition and its relation with pulmonary function and clinical manifestations. Patients and Methods: We studied 104 ex-smokers aged 69 ± 8 years (62 males) with mild to very severe COPD and 52 healthy non-smoker subjects aged 66 ± 11 years (13 males) as control group. High sensitivity serum C reactive protein (CRP), interleukin 6 (IL6), fibrinogen (F) and neutrophil count (Nc) were measured. Forced expiratory volume in the first minute (FEV1), inspiratory capacity (IC), arterial blood gases, six minutes walking test, dyspnea and body mass index (BMI) were measured, calculating the BODE index. Health status was assessed using the Saint George Respiratory Questionnaire (SGRQ), the chronic respiratory questionnaire (CRQ), registering the number of acute exacerbations (AE) during the previous year and inhaled steroids’s use. Systemic inflammation was considered present when levels of CRP or IL6 were above the percentile 95 of controls (7.98 mg/L and 3.42 pg/ml, respectively). Results: COPD patients had significantly higher CRP and IL6 levels than controls. Their F and Nc levels were within normal limits. Systemic inflammation was present in 56 patients, which had similar disease severity and frequency of inhaled steroid use, compared with patients without inflammation. Patients with systemic inflammation had more AE in the previous year; lower inspiratory capacity, greater dyspnea during the six minutes walk test and worse SGRQ and CRQ scores. Conclusions: Low-grade systemic inflammation was found in 56 of 104 ex-smokers with COPD. This group showed a greater degree of lung hyperinflation, dyspnea on exercise and poor quality of life.

Exacerbaciones en pacientes ex-fumadores con enfermedad pulmonar obstructiva crónica: efectos clínicos y funcionales a corto plazo / Short term effects of acute exacerbations in COPD patients

Acute exacerbations of COPD (AECOPD) are associated with decline of FEV1 and health related quality of life. Our aim was to evaluate the short-term effects of AECOPD on several functional and clinical indices in a cohort of 60 ex-smokers patients with COPD. During a 6-month follow up, 40 patients experienced one exacerbation (Group 1), mainly moderate, evaluated 30 days after by measuring BMI, dyspnea, FVC, FEV1, inspiratory capacity (IC), Sp02, six-min walking distance (6MWD), BODE index and quality of life (SGRQ). Values were compared with those measured at recruitment in stable conditions and with those obtained in the 20 patients without AECOPD during a similar period (Group 2). Baseline values were similar in both groups. Group 1 showed a significant worsening in FVC, FEV1, Sp02, BMI, 6MWD, and BODE index. Improvement in SGRQ and BODE was found in group 2. Significant differences in changes between groups were found for all variables, except IC and Sp02. The most noteworthy differences were found for BODE index (p = 0.001) and SGRQ (p = 0.004). Results demonstrate that moderate AECOPD produces significant short term functional and clinical impairment in ex-smokers COPD.

Las exacerbaciones de la EPOC deterioran el FEV1y la calidad de vida. Nuestro objetivo fue evaluar el efecto a corto plazo de las exacerbaciones sobre otros índices funcionales y clínicos. Sesenta pacientes ex fumadores con EPOC fueron seguidos durante 6 meses. Cuarenta presentaron una exacerbación (Grupo 1), generalmente moderada, estudiada 30 días después. los 20 pacientes no exacerbados constituyeron el grupo control (Grupo 2). Se midió IMC, disnea, CVF, FEV1h capacidad inspiratoria (CI), SpO2, caminata en 6 min (C6M), índice BODE y calidad de vida (SGRQ). En condiciones basales no hubo diferencias entre grupos. El grupo 1 empeoró CVF, VEF1, SpO2, IMC, C6M e índice BODE, sin cambios de CI ni SGRQ. El grupo 2 no presentó deterioro, mejorando SGRQ y BODE. Al comparar ambos grupos, hubo diferencias significativas en los cambios de todas las variables, excepto Cly SpO2, siendo estas diferencias más notorias en el índice BODE (p = 0,001) y SGRQ (p = 0,004). En suma, las exacerbaciones de la EPOC producen deterioro clínico y funcional significativo en el corto plazo.

Características clínicas y funcionales según género de pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional characteristics of COPD according to gender

Chronic obstructive pulmonary disease (COPD) prevalence is continuously rising in females. In addition, mortality due to COPD is higher in females, suggesting that women may develop a more severe disease than males. Our aim was to study possible differences in disease severity according to gender in 95 COPD patients (38 females) consecutively recruited to participate in a follow up protocol. Severity of COPD was assessed by FEV1, BODE index and the impairment of quality of life was measured with the Saint George's respiratory questionnaire (SGRQ) and the chronic respiratory questionnaire (CRQ). We found no differences according to gender in any of the severity indices studied. However, female smoked significantly less than males (35.5 +/- 19.4 versus 45.7 +/- 21 pack-year; p = 0.02). Our results suggest that women are more susceptible to develop COPD than men, without differences in disease severity.

La prevalencia, al igual que la mortalidad de la enfermedad pulmonar obstructiva crónica (EPOC), ha aumentado en las mujeres. Esto último sugiere que la enfermedad sería más grave en el sexo femenino. El propósito de este estudio fue evaluar si existen diferencias en la gravedad según género en 95 pacientes (38 mujeres) con EPOC ingresados consecutivamente a un protocolo de seguimiento. Evaluamos la magnitud del tabaquismo, características demográficas, gravedad según VEF1 e índice BODE y compromiso de la calidad de vida. Los resultados no demostraron diferencias entre hombres y mujeres en ninguno de los índices de gravedad. Sin embargo, la magnitud del tabaquismo fue inferior en las mujeres que en los hombres (35,5 +/- 19,4 vs 45,7 +/- 21 paquetes-año; p = 0,02). Nuestros resultados sugieren una mayor susceptibilidad de las mujeres para desarrollar EPOC, pero no demuestran que la gravedad de la enfermedad dependa del género.

Beneficios clínicos y funcionales de agregar teofilina a la terapia inhalatoria con broncodilatadores de acción corta en pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD

Background: Although theophylline is considered a third line bronchodilator drug for the treatment of chronic obstructive pulmonary disease (COPD), it is widely used in Chile, because it is administered orally and has a moderate cost. Aim: To evaluate if theophylline adds clinical and/or functional benefits when associated to standard recommended inhaled bronchodilator therapy. Subjects and methods: Thirty-eight stable COPD patients who accepted to participate in the study approved by the Ethics Committee of our institution were studied. Using a randomized double-blind placebo-controlled study, theophylline (250 mg) or placebo was administered twice a day for 15 days in addition to inhaled salbutamol and ipratropium bromide. Prior to and at the end of the study, patients underwent: a) a spirometry to evaluate changes in dynamic pulmonary hyperinflation using slow vital capacity (SVC) and inspiratory capacity (IC), b) the 6 min walking distance (6 MWD); and c) measurement of maximal inspiratory and expiratory pressures. Dyspnea and quality of life (QoL) were evaluated using appropriate questionnaires. Results: Compared to placebo, patients on theophylline showed significant increases in SVC (p=0.014), IC (p=0.002), and 6 MWD (p=0.005). They also experienced an improvement in dyspnea (p=0.042) and QoL (p=0.011). All patients improved at least one of these parameters with 53% of the patients showing an improvement in 3 or more. Conclusions: Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL.

Etiología de la neumonía adquirida en la comunidad en adultos hospitalizados en Santiago, Chile: implicancias para las guías clínicas / Etiology of community acquired pneumonia requiring hospitalization in Chile: implications for the guidelines

Background: There are a few studies examining the etiology of community acquired pneumonia (CAP) in Chile. Aim: To evaluate the etiology of CAP in hospitalized adults. Method: We prospectively studied 130 patients (mean age +/- SD: 68 +/- 18 y.o.; overall hospital mortality: 6.2 percent), over a 16 month period. Microbiological evaluation included blood and sputum cultures for bacteria; serology for C. pneumoniae, C. psittaci and M. pneumoniae; urine antigen for L. pneumophila; and nasopharyngeal swab for respiratory viruses. Results: Etiology was identified from 64 (49 percent) patients (two or more pathogens in 6). The most frequent microorganisms were S. pneumoniae (34 percent), Parainfluenza types 1 to 3 (22 percent), Influenza A or B (14 percent ), C. pneumoniae (6 percent), M. pneumoniae (6 percent), H. influenzae (5 percent) and S. marcescens (5 percent). Twenty-five of 27 (93 percent) respiratory viruses were identified in autumn or winter. Pneumococcal pneumonia patients (19) compared to those infected with respiratory virus (23) were younger (59 +/- 18 versus 72 +/- 17 y.o.; p = 0.021) and had less comorbidities (47 versus 87 percent; p = 0.0001). No patients with bacteremia (13 of 121: 11 percent) died. Conclusions: S. pneumoniae remains the most important pathogen to cover by initial antibiotic therapy; the second most frequent etiological agents were respiratory viruses followed by "atypical pathogens". Recommendations for the management of patients infected with these two last categories of agents should be included in future national guidelines.

Fundamento: Hay escasos estudios que examinen la etiología de la neumonía adquirida en la comunidad (NAC) en población adulta chilena. Objetivo: Identificar la etiología de la NAC en adultos inmunocompetentes hospitalizados. Método: Estudiamos, prospectiva y consecutivamente durante 16 meses, a 130 pacientes (edad promedio +/ - DS: 68 +/ - 18 años; letalidad en el hospital: 6,2 por ciento). La evaluación microbiológica incluyó cultivo de expectoración y hemocultivos para bacterias; Financiamiento: Fondo de Investigación de la Sociedad Chilena de Enfermedades Respiratorias (2002) y fondo de la Dirección de Investigación de la Pontificia Universidad Católica de Chile (DIPUC 2003/10E). Serología para C. pneumoniae, C. psittaci, M. pneumoniae; antígeno urinario para L. pneumophila e hisopado nasofaríngeo para virus respiratorios. Resultados: Se identificó la etiología en 64 (49 por ciento) pacientes (dos o más patógenos en 6). Los principales microorganismos fueron: S. pneumoniae (34 por ciento), virus Parainfluenza 1 a 3 (22 por ciento), virus Influenza A o B (14 por ciento), C. pneumoniae (6 por ciento), M. pneumoniae (6 por ciento), H. influenzae (5 por ciento) y S. marcescens (5 por ciento). El 93 por ciento (25/27) de los virus respiratorios se identificaron en otoño-invierno. Los pacientes con neumonía neumocócica (19) comparados con aquéllos infectados por virus respiratorios (23) eran más jóvenes (59 + /- 18 versus 72 +/ - 17 años; p = 0,021) y tenían menos comorbilidades (47 por ciento versus 87 por ciento; p = 0,0001). Ninguno de los 13 (11 por ciento) pacientes con bacteremia falleció en el hospital. Conclusiones: S. pneumoniae sigue siendo el principal patógeno a cubrir por el tratamiento antibiótico empírico; los virus respiratorios y los agentes atípicos fueron los que siguieron en frecuencia. Las futuras guías clínicas nacionales deberían incluir recomendaciones para el manejo de los pacientes infectados por estos dos últimos grupos de...