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Both systemic inflammation and exacerbations have been associated with greater severity of bronchiectasis. Our objective was to analyze the prognostic value of the peripheral concentration of C-reactive protein (CRP) for the number and severity of exacerbations in patients with bronchiectasis.Patients from the Spanish Bronchiectasis Registry (RIBRON) with valid data on their CRP value (in a clinically stable phase) and valid data on exacerbations during the first year of follow-up were included. A logistic regression analysis was used to evaluate the prognostic value of the CRP concentration (divided into tertiles) with the presence of at least one severe exacerbation or at least two mild-moderate exacerbations during the first year of follow-up.802 patients (mean age: 68.1 [11.1 years], 65% female) were included. Of these, 33.8% and 13%, respectively, presented ≥2 mild-moderate exacerbations or at least one severe exacerbation during the first year of follow-up. The mean value of the CRP was 6.5 (17.6mg/L). Patients with a CRP value between 0.4 and 2.7mg/L (second tertile) and ≥2.7mg/L (third tertile) presented a 2.9 (95%CI: 1.4-5.9) and 4.2 (95%CI: 2.2-8.2) times greater probability, respectively, of experiencing a severe exacerbation than those with0.4mg/L (control group), regardless of bronchiectasis severity or a history of previous exacerbations. However, the CRP value did not present any prognostic value for the number of mild-moderate exacerbations.The CRP value was associated with a greater risk of future severe exacerbations but not with mild or moderate exacerbations in patients with steady-state bronchiectasis.

Resumen A pesar de que es conocido que la presencia cronica de microorganismos en las vias aereas de pacientes con enfermedad pulmonar obstructiva cronica (EPOC) en fase de estabilidad conlleva una evolucion desfavorable, ninguna guia de manejo de la enfermedad establece pautas sobre como diagnosticar y tratar este tipo de casos. Con la intencion de orientar a los profesionales, desde la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) se ha elaborado un documento que pretende aportar respuestas clinicas sobre el manejo de pacientes con EPOC en los que se aislan microorganismos de forma puntual o persistente. Dado que la heterogeneidad de las evidencias cientificas disponibles no permite crear una Guia de Practica Clinica, se ha elaborado un documento basado en la literatura cientifica existente y/o en la propia experiencia clinica que aborda tanto la definicion de las diferentes situaciones clinicas como su diagnostico y manejo. El texto ha sido consensuado entre un amplio numero de neumologos con gran experiencia clinica y cientifica en este ambito. Este documento cuenta con el aval del Comite Cientifico de SEPAR.

Resumen En la mayoria de los ambitos de la neumologia se sigue utilizando un principio osleriano (basado en los sintomas y signos) en los que la enfermedad es el centro de toda actividad, pero este paradigma esta cambiando. Actualmente, gracias al reconocimiento de la heterogeneidad y complejidad de las enfermedades pulmonares, la tendencia es a realizar una medicina mas personalizada, de precision, o centrada en el paciente. En la presente revision se intentara establecer la situacion actual sobre el conocimiento de las bronquiectasias, o mejor, del sindrome bronquiectasico, como una enfermedad multidimensional, sistemica, heterogenea y compleja, los pasos que ya se han dado en este sentido, y sobre todo, en los muchos que quedan por dar. Asimismo, se propondran algunas herramientas que podrian facilitar la traslacion de estos conceptos a la practica clinica, y con ellos seguir avanzando hacia una imagen mas holistica de esta enfermedad.

Introduction: Bronchiectasis is a very heterogeneous disease but some homogeneous groups with similar clinical characteristics and prognosis have been identified. Exacerbations have been shown to have a negative impact on the natural history of bronchiectasis. The objective of this study was to identify the definition and characteristics of the "frequent exacerbator patient" with the best prognostic value and its relationship with the severity of bronchiectasis. Methods: A historical cohort of 651 patients diagnosed with bronchiectasis was included. They had all received 5 years of follow-up since their radiological diagnosis. Exacerbation was defined as a worsening of the symptoms derived from bronchiectasis that required antibiotic treatment. The main outcome was all-cause mortality at the end of follow-up. Results: The mean age was 48.2 (16) years (32.9% males). 39.8% had chronic infection by Pseudomonas aeruginosa. Mean BSI, FACED, and E-FACED were 7 (4.12), 2.36 (1.68), and 2.89 (2.03), respectively. There were 95 deaths during follow-up. The definition of the "frequent exacerbator patient" that presented the greatest predictive power for mortality was based on at least two exacerbations/year or one hospitalization/year (23.3% of patients; AUC-ROC: 0.75 [95% CI: 0.69-0.81]). Its predictive power was independent of the patient's initial severity. The clinical characteristics of the frequent exacerbator patient according to this definition varied according to the initial severity of bronchiectasis, presence of systemic inflammation, and treatment. Conclusions: The combination of two exacerbations or one hospitalization per year is the definition of frequent exacerbator patient that has the best predictive value of mortality independent of the initial severity of bronchiectasis. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Resumen En 2008, la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) publico las primeras normativas del mundo sobre el diagnostico y tratamiento de las bronquiectasias. Tras casi una decada, muchos han sido los avances cientificos en esta enfermedad, tanto en sus aspectos terapeuticos como en su valoracion y diagnostico. Por ello estas nuevas normativas sobre el tratamiento de las bronquiectasias en el adulto tratan de ofrecer al lector una actualizacion del conocimiento cientifico sobre las posibilidades terapeuticas en bronquiectasias, basandose en un estricto procedimiento metodologico que asegura la calidad del contenido de la misma, y en una amplia cantidad de informacion online que incluye abundante bibliografia. En estas normativas se ha enfocado el tratamiento de las bronquiectasias desde un punto de vista tanto multidisciplinar, que implica las especialidades y escalones asistenciales involucrados, como multidimensional que incluye todos y cada uno de los aspectos que definen a la enfermedad. Asi, se establecen recomendaciones basadas en una exhaustiva revision de la evidencia sobre los tratamientos de la etiologia, de la infeccion bronquial en sus diferentes formas de presentacion y con las diferentes terapias existentes, de la inflamacion bronquial y de la obstruccion al flujo aereo. Se revisan los aspectos nutricionales, el manejo de las secreciones, el entrenamiento muscular, el manejo de las complicaciones y comorbilidades, la profilaxis de la infeccion, los aspectos educacionales, el manejo del paciente en el domicilio, el tratamiento quirurgico, las agudizaciones y el seguimiento de los pacientes.

In 2008, the Spanish Society of Pulmonology (SEPAR) published the first guidelines in the world on the diagnosis and treatment of bronchiectasis. Almost 10 years later, considerable scientific advances have been made in both the treatment and the evaluation and diagnosis of this disease, and the original guidelines have been updated to include the latest scientific knowledge on bronchiectasis. These new recommendations have been drafted following a strict methodological process designed to ensure the quality of content, and are linked to a large amount of online information that includes a wealth of references. These guidelines cover aspects ranging from a consensual definition of bronchiectasis to an evaluation of the natural course and prognosis of the disease. The topics of greatest interest and some new areas are addressed, including epidemiology and economic costs of bronchiectasis, pathophysiological aspects, the causes (placing particular emphasis on the relationship with other airway diseases such as chronic obstructive pulmonary disease and asthma), clinical and functional aspects, measurement of quality of life, radiological diagnosis and assessment, diagnostic algorithms, microbiological aspects (including the definition of key concepts, such as bacterial eradication or chronic bronchial infection), and the evaluation of severity and disease prognosis using recently published multidimensional tools.

Bronchiectasis; Quality of life; Respiratory disease Bronquiectasia; Calidad de vida; Enfermedad respiratoria Bronquiectàsia; Qualitat de vida; Malaltia respiratòria Cough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George’s Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach’s α 0.81–0.93). The test–retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was −0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations. The author(s) received no financial support for the research, authorship, and/or publication of this article.

Background: The excessive retention of sputum in the airways, leading to pulmonary infections, is a common consequence of bronchiectasis. Although inhalation of 7% hypertonic saline (HS) has proven an effective method to help remove the mucus, many patients are intolerant of this treatment. The addition of 0.1% hyaluronic acid to HS (HS+HA) could increase tolerance to HS in these patients. The main objective of this study was to evaluate the tolerability of HS+HA in bronchiectasis patients who are intolerant to HS. Methods: This prospective, observational, open-label study analysed the outcomes of two groups of bronchiectasis patients previously scheduled to start HS therapy. Patients were assessed for tolerance to HS by a questionnaire, spirometry and clinical evaluation. Patients who were intolerant were evaluated for tolerance to HS+HA approximately one week later. All patients were evaluated for their tolerance to HS or HS+HA 4 weeks after the start of their treatment. Patients were also assessed with quality-of-life and adherence questionnaires, and all adverse events were registered. Results: A total of 137 bronchiectasis patients were enrolled in the study (age = 63.0 ± 14.7 years; 63.5% women). Of these, 92 patients (67.1%) were tolerant and 45 patients (32.9%) were intolerant to HS. Of the 45 patients intolerant to HS, 31 patients (68.9%) were tolerant and 14 patients (31.1%) intolerant to HS+HA. Of these 31 tolerant patients, 26 (83.9%) could complete the 4-week treatment with HS+HA. Conclusions: Two-thirds of bronchiectasis patients that presented intolerance to inhaled HS alone are tolerant to inhaled HS+HA, suggesting that HA improves tolerance to HS therapy.

Background Glycosaminoglycans (GAGs) are essential in many infections, including recurrent bacterial respiratory infections, the main cause of mortality in cystic fibrosis (CF) patients. Methods Using a cellular model of healthy and CF lung epithelium, a comparative transcriptomic study of GAG encoding genes was performed using qRT-PCR, and their differential involvement in the adhesion of bacterial pathogens analyzed by enzymatic degradation and binding competition experiments. Results Various alterations in gene expression in CF cells were found which affect GAG structures and seem to influence bacterial adherence to lung epithelium cells. Heparan sulfate appears to be the most important GAG species involved in bacterial binding. Conclusions Adherence to lung epithelial cells of some of the main pathogens involved in CF is dependent on GAGs, and the expression of these polysaccharides is altered in CF cells, suggesting it could play an essential role in the development of infectious pathology.

Resumen Pseudomonas aeruginosa es el patogeno mas importante en la infeccion broncopulmonar en fibrosis quistica (FQ). Solo se erradica en la infeccion inicial, mientras que la reduccion de su carga bacteriana es el objetivo terapeutico en la infeccion cronica y exacerbaciones. El cribado neonatal y la farmacocinetica/farmacodinamica han cambiado el manejo del paciente con FQ. Se debe realizar un seguimiento microbiologico en los pacientes sin infeccion por P. aeruginosa. En la infeccion inicial se recomienda tratamiento inhalado (28 dias) con colistina (0,5-2 MU/8 h), tobramicina (300 mg/12 h) o aztreonam (75 mg/8 h) con o sin ciprofloxacino oral (15-20 mg/kg/12 h, 2-3 semanas). En la infeccion cronica se recomienda solo via inhalada en tratamiento continuo con colistina, o en ciclos on-off de 28 dias con tobramicina o aztreonam. Durante las exacerbaciones leves-moderadas se recomienda tratamiento oral (ciprofloxacino, 2-3 semanas) y en las graves tratamiento intravenoso (β-lactamico asociado a un aminoglicosido o una fluoroquinolona). Estudios futuros sustentaran la rotacion y nuevas combinaciones de antimicrobianos. Se deben establecer tambien medidas epidemiologicas que eviten nuevas infecciones y la transmision cruzada de P. aeruginosa.

Background: Information on the role of fungi in non-cystic fibrosis (CF) bronchiectasis is lacking. Objectives: Our aim was to determine the prevalence of and factors associated with the isolation and persistence of fungi from sputum in these patients. Methods: We performed a multicenter observational study comprising adult patients with non-CF bronchiectasis. Persistence of Aspergillus spp. and Candida albicans was defined as the presence of ≥2 positive sputum cultures taken at least 6 months apart within a period of 5 years. Results: A total of 252 patients (62.7% women with a mean ± SD age of 55.3 ± 16.7 years) were included in the study. All patients had at least 1 sputum sample cultured for fungi, with a mean ± SD of 7 ± 6 cultures per patient. Eighteen (8.7%) and 71 (34.5%) patients had persistent positive cultures for Aspergillus spp. and C. albicans, respectively. Patients with persistence of Aspergillus spp. and C. albicans were older and had more daily purulent sputum. In addition, patients with persistent C. albicans had worse postbronchodilator forced expiratory volume in the first second (FEV1), more frequent cystic bronchiectasis, and more hospital-treated exacerbations. They were also more frequently treated with long-term antibiotics. Multivariate analysis showed that daily purulent sputum (OR = 3.75, p = 0.045) and long-term antibiotics (OR = 2.37, p = 0.005) were independently associated with persistence of Aspergillus spp. and C. albicans, respectively. Conclusions: Isolation and persistence of Aspergillus spp. and C. albicans are frequent in patients with non-CF bronchiectasis. Daily purulent sputum and chronic antibiotic treatment were associated with persistence of Aspergillus spp. and C. albicans, respectively.

Background The FACED score is an easy-to-use multidimensional grading system that has demonstrated an excellent prognostic value for mortality in patients with bronchiectasis. A Spanish group developed the score but no multicenter international validation has yet been published. Methods Retrospective and multicenter study conducted in six historical cohorts of patients from Latin America including 651 patients with bronchiectasis. Clinical, microbiological, functional, and radiological variables were collected, following the same criteria used in the original FACED score study. The vital status of all patients was determined in the fifth year of follow-up. The area under ROC curve (AUC-ROC) was used to calculate the predictive power of the FACED score for all-cause and respiratory deaths and both number and severity of exacerbations. The discriminatory power to divide patients into three groups of increasing severity was also analyzed. Results Mean (SD) age of 48.2 (16), 32.9% of males. The mean FACED score was 2.35 (1.68). During the follow up, 95 patients (14.6%) died (66% from respiratory causes). The AUC ROC to predict all-cause and respiratory mortality were 0.81 (95% CI: 0.77 to 0.85) 0.84 (95% CI: 0.80 to 0.88) respectively, and 0.82 (95% CI: 078–0.87) for at least one hospitalization per year. The division into three score groups separated bronchiectasis into distinct mortality groups (mild: 3.7%; moderate: 20.7% and severe: 48.5% mortality; p

Patients with bronchiectasis (BE) present exacerbations that increase with severity of the disease. We aimed to determine the annual cost of BE treatment according to its severity, determined by FACED score, as well as the parameters associated with higher costs. Multicentre historical cohorts study with patients from six hospitals in Spain. The costs arising during the course of a year from maintenance treatment, exacerbations, emergency visits and hospital admissions were analysed. In total, 456 patients were included (56.4% mild BE, 26.8% moderate BE and 16.9% severe BE). The mean cost was €4671.9 per patient, which increased significantly with severity. In mild BE, most of the costs were due to bronchodilators and inhaled steroids; in severe BE, most were due to exacerbations and inhaled antibiotics. Forced expiratory volume in 1 second (FEV1%), age, colonization by Pseudomonas aeruginosa and the number of admissions were independently related to higher costs. The highest costs were found in patients with BE associated with chronic obstructive pulmonary disease, with the most exacerbations and with chronic bronchial colonization by Pseudomonas aeruginosa (PA). In conclusion, BE patients gave rise to high annual costs, and these were doubled on each advance in severity on the FACED score. FEV1%, age, colonization by PA and the number of admissions were independently related to higher costs.

Rationale: Exacerbations are relevant in bronchiectasis (BE) but little is known regarding microbiology and outcomes of pneumonic (CAP) vs. non-pneumonic (EXAC) exacerbations Objective: To compare clinical and microbiological characteristics of CAP vs. EXAC in adult patients with BE Methods: Multicentre prospective observational study of consecutive cases from 4 Spanish hospitals Results: We recruited 144 patients: 91 EXAC (63%) and 53 CAP (37%); 89% required hospitalization (CAP 94%, EXAC 86%). Demographics, vaccines, bronchiectasis aetiology and severity, and lung function were similar in both groups. CAP group showed more males and COPD but less chronic bronchial infection, previous exacerbations and macrolides than EXAC group. Clinical presentation was similar excepting higher values of creatinine, C-reactive protein, glucose and leukocytes in CAP. S.pneumoniae and P.aeruginosa were the first cause of CAP and EXAC, respectively. Most patients with P.aeruginosa already had a chronic infection by the same microorganism prior to CAP (71%) or EXAC (81%). Nevertheless, numerous patients with previous chronic P.aeruginosa had a new infection in our study (19% of EXAC, 58% of CAP). CAP showed more atrial fibrillation but similar outcomes (hospital stay, mortality, etc.) than EXAC. Chronic bronchial infection and previous exacerbations≥2/year were protective factors for CAP at multivariate analysis Conclusions : CAP and EXAC in patients with BE have similar clinical presentation.An initial antibiotic treatment should cover S.pneumoniae in CAP and P.aeruginosa in EXAC, particularly in case of previous chronic infection, however a complete microbiological research is recommended. Pneumococcal vaccination should be considered in BE.

The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are both very heterogeneous.To identify different clinical phenotypes for non-cystic fibrosis bronchiectasis and their impact on prognosis.Using a standardized protocol, we conducted a multicenter observational cohort study at six Spanish centers with patients diagnosed with non-cystic fibrosis bronchiectasis before December 31, 2005, with a 5-year follow-up from the bronchiectasis diagnosis. A cluster analysis was used to classify the patients into homogeneous groups by means of significant variables corresponding to different aspects of bronchiectasis (clinical phenotypes): age, sex, body mass index, smoking habit, dyspnea, macroscopic appearance of sputum, number of exacerbations, chronic colonization with Pseudomonas aeruginosa, FEV1, number of pulmonary lobes affected, idiopathic bronchiectasis, and associated chronic obstructive pulmonary disease. Survival analysis (Kaplan-Meier method and log-rank test) was used to evaluate the comparative survival of the different subgroups.A total of 468 patients with a mean age of 63 (15.9) years were analyzed. Of these, 58% were females, 39.7% had idiopathic bronchiectasis, and 29.3% presented with chronic Pseudomonas aeruginosa colonization. Cluster analysis showed four clinical phenotypes: (1) younger women with mild disease, (2) older women with mild disease, (3) older patients with severe disease who had frequent exacerbations, and (4) older patients with severe disease who did not have frequent exacerbations. The follow-up period was 54 months, during which there were 95 deaths. Mortality was low in the first and second groups (3.9% and 7.6%, respectively) and high for the third (37%) and fourth (40.8%) groups. The third cluster had a higher proportion of respiratory deaths than the fourth (77.8% vs. 34.4%; P 0.001).Using cluster analysis, it is possible to separate patients with bronchiectasis into distinct clinical phenotypes with different prognoses.

The Leicester Cough Questionnaire (LCQ) has been validated in non-cystic fibrosis bronchiectasis (NCFBC). The present study aimed to create and validate a Spanish version of the LCQ (LCQ-Sp) in NCFBC. The LCQ-Sp was developed following a standardized protocol. For reliability, we assessed internal consistency and the change in score over a 15-day period in stable state. For responsiveness, we assessed the change in scores between visit 1 and the first exacerbation. For validity, we evaluated convergent validity through correlation with the Saint George’s Respiratory Questionnaire (SGRQ) and discriminant validity. Two hundred fifty-nine patients (118 mild bronchiectasis, 90 moderate bronchiectasis and 47 severe bronchiectasis) were included. Internal consistency was high for the total scoring and good for the different domains (Cronbach’s α: 0.86–0.91). The test–retest reliability shows an intraclass correlation coefficient of 0.87 for the total score. The mean LCQ-Sp score at visit 1 decreased at the beginning of an exacerbation (15.13 ± 4.06 vs. 12.24 ± 4.64; p < 0.001). The correlation between LCQ-Sp and SGRQ scores was −0.66 ( p < 0.01). The differences in the LCQ-Sp total score between the different groups of severity were significant ( p < 0.001). The LCQ-Sp discriminates disease severity, is responsive to change when faced with exacerbations and is reliable for use in bronchiectasis.

Resumen La neumonitis por hipersensibilidad o alveolitis alergica extrinseca (AAE) se origina por una reaccion de hipersensibilidad a antigenos inhalados sobre un pulmon con una susceptibilidad individual. En el caso del pulmon del cuidador de aves, son particulas que suelen encontrarse en el epitelio, el polvo que cubre las plumas o las heces de las aves. En la exploracion fisica destacan los crepitantes inspiratorios a la auscultacion pulmonar y los hallazgos en la radiografia de torax pueden ser muy variables. La TC nos muestra diferentes patrones en funcion de la fase de la enfermedad en que nos encontremos. Respecto a las pruebas de funcion respiratoria, la mayoria de los pacientes presenta un patron restrictivo. Un diagnostico precoz sera crucial en la evolucion de la enfermedad, ya que la progresion puede conducir a una fibrosis pulmonar o una enfermedad pulmonar obstructiva cronica. Lo principal es eliminar la exposicion a los antigenos, con ello muchos pacientes se recuperan.

Resumen La hipertension pulmonar (HP) es una condicion hemodinamica que se define por un aumento de la presion media de la arteria pulmonar mayor de 25 mmHg en reposo, medida por cateterismo cardiaco derecho. El aumento progresivo de la resistencia vascular pulmonar (RVP) conduce al fallo del ventriculo derecho y a la muerte prematura, con una esperanza de vida media con tratamiento convencional de 2,8 anos. Se ha producido una modificacion en la clasificacion de la HP, en cinco subgrupos, clinicos basadas, fundamentalmente, en las caracteristicas clinicas de las mismas y en las opciones terapeuticas para cada grupo. El diagnostico de esta enfermedad es dificil debido a su rareza, con una prevalencia de 15 casos por millon de habitantes, y a lo inespecifico de los sintomas, lo que produce un retraso en el mismo de meses o anos. Por ese motivo se ha propuesto un algoritmo diagnostico. La estrategia en el tratamiento es distinto segun los diferentes grupos y el perfil “de riesgo”. Los avance logrados en el tratamiento, las nuevas perspectivas terapeuticas en investigacion, la aplicacion en la practica clinica de consensos y guias, nos permitiran un manejo homogeneo y multidisciplinario, para poder llegar al tan esperado cambio en el pronostico de esta enfermedad.

Resumen El sindrome platipnea-ortodesoxia (SPO) se caracteriza por disnea e hipoxemia en ortostatismo que remite al adoptar el decubito supino. Las causas pueden ser cardiacas o pulmonares. Las cardiacas se deben a un circuito derecha-izquierda que se hace mas evidente al incorporarse, cuando aumenta la cantidad de sangre desoxigenada que confluye a la circulacion sistemica. Las causas pulmonares se deben a un circuito vascular (fistulas arteriovenosas pulmonares o sindrome hepatopulmonar), cuando en ortostatismo la gravedad aumenta el flujo en las bases pulmonares, o a un circuito parenquimatoso (enfisema pulmonar, neumonectomias, embolismos pulmonares o sindrome de distres respiratorio del adulto), si la afectacion es predominante en bases, al incrementarse el espacio muerto por hematosis ineficaz. El SPO es un fenomeno mas comun de lo que parece, y su diagnostico ha aumentado, no solo por la mejoria de las tecnicas diagnosticas, sino porque se piensa en el y se incluye en los diagnosticos diferenciales.

OBJETIVO: Evaluar la prevalencia de micobacterias ambientales (MA) en pacientes con fibrosis quistica (FQ). PACIENTES Y METODOS: Se ha realizado un estudio prospectivo de 2 anos de duracion en pacientes con FQ mayores de 6 anos, procedentes de 6 unidades monograficas. En las muestras respiratorias, recogidas cada 6 meses, se efectuo una tincion de auramina-rodamina, ademas de cultivos en medios solido y liquido. Si se detectaba una tincion o cultivo positivo para MA, se recogian 1 o 2 esputos mas y se hacia un seguimiento estricto para valorar la necesidad de tratamiento especifico. Se consideraron las siguientes variables clinicas: edad, sexo, insuficiencia pancreatica, diabetes, uso de aerosolterapia antibiotica y de azitromicina de forma continua, tratamientos con corticoides inhalados o por via oral de forma prolongada. RESULTADOS: Participaron en el estudio 220 pacientes (119 mujeres), con una edad media de 22,62 anos (rango: 6-74). El 23,6% recibia azitromicina. Se cultivaron para la deteccion de micobacterias 1.303 muestras de esputo (rango por paciente: 4-68), de las que la tincion de auramina fue positiva en 17 casos y el cultivo en 48, correspondientes a 17 pacientes (7,72%). En 88 muestras el cultivo estaba contaminado. En ningun caso se aislo Mycobacterium tuberculosis. Las MA aisladas fueron: M. avium complex (n = 10), M. abscessus (n = 6) y M. fortuitum (n = 1). Cinco de los 9 pacientes que presentaron mas de un aislamiento tuvieron deterioro clinico y se les indico tratamiento especifico. No hubo diferencias entre las variables clinicas de los pacientes con y sin aislamientos de MA. CONCLUSIONES: La prevalencia de MA en pacientes con FQ no fue muy alta (7,72%), quiza debido a la interferencia de la azitromicina sobre el crecimiento de MA. Hay que vigilar estrechamente a los pacientes con aislamientos repetidos.

Bronchiectasis is the end result of several different diseases that share principles of management. The clinical course usually involves chronic bronchial infection and inflammation, which are associated with progression. The cause of bronchiectasis should always be investigated, particularly when it can be treated. We recommend evaluating etiology, symptoms, bronchial colonization and infection, respiratory function, inflammation, structural damage, nutritional status, and quality of life in order to assess severity and to monitor clinical course. Care should be supervised by specialized units, at least in cases of chronic bronchial infection, recurrent exacerbations, or when there is a cause that is likely to respond to treatment. Improving symptoms and halting progression are the goals of management, which is based on treatment of the underlying cause and of acute or chronic infections and on the drainage of secretions. Complications that arise must also be treated. Antibiotic prescription is guided by how well infection is being controlled, and this is indicated by the color of sputum and a reduction in the number of exacerbations. We recommend inhaled antibiotics in cases of chronic bronchial infection that does not respond to oral antibiotics, when these cause side effects, or when the cause is Pseudomonas species or other bacteria resistant to oral antibiotics. Inhaled administration is also advisable to treat initial colonization by Pseudomonas species.

El aislamiento de Nocardia spp. en las secreciones respiratorias de los pacientes con fibrosis quistica (FQ) plantea problemas en cuanto a su trascendencia clinica. De un total de 387 pacientes con FQ, se aislo Nocardia spp. en el cultivo de esputo en 9 (2%; 8 mujeres y un varon), con una edad media ( ± desviacion estandar) de 17 ± 7 anos. El 67% de los casos se encontraba asintomatico y en ningun paciente se detectaron cambios radiologicos ni analiticos de interes. En solo 3 pacientes el aislamiento se repitio en muestras sucesiva. Dos pacientes no fueron tratados y en los restantes se empleo cotrimoxazol (7 casos), minociclina (3 casos) y tratamiento intravenoso (2 casos). Despues de un seguimiento de 48 ± 33 meses, todos los pacientes presentaron una evolucion clinica favorable. El aislamiento de Nocardia spp. en pacientes con FQ no implica necesariamente infeccion y la necesidad de tratamiento debe valorarse individualmente.

La polimiositis es una colagenopatia rara, que puede afectar al pulmon. Entre un 5 y un 30% de los pacientes con polimiositis presenta una enfermedad pulmonar intersticial en el momento del diagnostico o durante el curso de la enfermedad. El inicio suele ser insidioso en forma de disnea y tos seca. Son varias las entidades histopatologicas que se asocian a polimiositis, de las cuales la mas frecuente es la neumonia intersticial no especifica. El pronostico de la enfermedad pulmonar intersticial difusa asociada a polimiositis es mejor que el de la fibrosis pulmonar idiopatica, ya que la mayoria de los pacientes responde al tratamiento con glucocorticoides e inmunodepresores. Presentamos el caso clinico de una mujer de 60 anos con sintomas de disnea y debilidad muscular, a quien se diagnostico de polimiositis y enfermedad pulmonar intersticial difusa (posible neumonia intersticial no especifica por hallazgos radiologicos), y que mostro buena respuesta al tratamiento con prednisona y metotrexato.

Objetivo: Los pacientes con fibrosis quistica (FQ) presentan un mayor riesgo de infeccion por micobacterias ambientales en relacion con ciertos factores predisponentes como bronquiectasias, desnutricion y diabetes. El objetivo del presente estudio es analizar los resultados de las baciloscopias y cultivos de micobacterias de esputos de pacientes con FQ de una unidad de adultos, entre marzo de 1997 y diciembre de 2001. Pacientes y metodos: Las muestras de esputo se recogieron de forma prospectiva y protocolizada en cada visita y en la mayoria de las exacerbaciones, en las que, ademas de los cultivos bacterianos habituales y de hongos, se solicitaron tincion y cultivo para micobacterias. Se realizo la prueba de la tuberculina al final del estudio. Resultados: Se incluyo a 28 pacientes con FQ, 16 varones, con una edad media (± DE) de 25,3 ± 6,7 anos. Se cultivaron un total de 251 muestras (rango por paciente de 1 a 31). El tiempo medio de seguimiento fue de 40,3 ± 22,1 meses. En 29 casos (4 pacientes) la baciloscopia fue positiva y se obtuvieron cultivos positivos en 7 pacientes, solo en 4 en mas de 3 muestras. Se aislaron: Mycobacterium abscessus en 3 casos, M. avium complex en 2 y M. simiae en uno y en otro una especie de crecimiento rapido no identificada. En 5 pacientes el Mantoux fue positivo. Dos de los 4 pacientes con aislamientos reiterados presentaron deterioro clinico y requirieron tratamiento. Conclusiones: Hay una alta prevalencia de micobacterias ambientales en pacientes con FQ. Habria que realizar tincion y cultivo para micobacterias de forma periodica y en caso de exacerbacion pulmonar no atribuible a infeccion bacteriana habitual. Hay que vigilar estrechamente a los pacientes con aislamientos repetidos.

La enfermedad de Wegener es una vasculitis granulomatosa sistemica de etiologia desconocida, que afecta sobre todo al tracto respiratorio superior e inferior y al rinon, aunque se distingue una forma limitada al pulmon. Es una entidad poco frecuente, con una incidencia estimada de 8,5 por 1.000.000 de habitantes/ano. Los principales sintomas de comienzo suelen ser los derivados de la afectacion de las vias aereas superior e inferior. El sistema nervioso central se implica en alrededor de un 22% de los casos, pero es infrecuente que la clinica neurologica forme parte de la sintomatologia inicial. Los anticuerpos anticitoplasma del neutrofilo especificos contra la proteinasa 3 constituyen marcadores serologicos de gran utilidad para el establecimiento del diag- nostico, aunque este debe confirmarse por la biopsia tisular del organo afectado.

La linfangioleiomiomatosis (LAM) es una enfermedad pulmonar rara que afecta a mujeres jovenes y que suele progresar hacia el fracaso del sistema respiratorio. No existe evidencia cientifica suficiente que justifique el uso de ningun farmaco en la LAM. El unico tratamiento efectivo en los casos graves es el trasplante pulmonar. En la LAM se ha observado una activacion de mammalian target of rapamycin (mTOR). La administracion de sirolimus, un inhibidor de mTOR, parece reducir los angiomiolipomas renales que se asocian a la LAM. Ademas, algunos trabajos sugieren una mejoria de la funcion pulmonar con este farmaco. Presentamos tres mujeres con LAM que manifestaron un deterioro clinico y funcional respiratorio rapidamente progresivo y que fueron tratadas con sirolimus.

Resumen Las alteraciones anatomicas de la via aerea son un factor de riesgo para desarrollar un sindrome de apnea-hipopnea del sueno (SAHS). Presentamos un caso clinico de un paciente con estenosis traqueal y masa en lengua que desarrolla un SAHS que evoluciono favorablemente con ventilacion mecanica no invasora.

Resumen La inmunodeficiencia comun variable (CVID) es la inmunodeficiencia primaria que con mas frecuencia encontramos en la practica clinica. Clinicamente se define como la presencia de infecciones recurrentes y una reduccion en suero de IgG (al menos 2 desviaciones estandar por debajo de los valores de referencia para su edad) y al menos otra de las Ig (IgA o IgM) y una reduccion o ausencia de produccion de titulos protectores de anticuerpos para vacunas de polisacaridos y antigenos proteicos. La clinica que presentan estos pacientes son multiples infecciones sinopulmonares, infecciones bacterianas sistemicas y complicaciones gastrointestinales, siendo las infecciones sinopulmonares la manifestacion clinica con que se presenta mayoritariamente. El pilar principal del tratamiento de la CVID es el tratamiento sustitutivo con inmunoglobulinas, junto con los antibioticos para las infecciones y el tratamiento adecuado de las complicaciones no infecciosas.

La fibrosis quistica (FQ) es una enfermedad multisistemica que afecta a glandulas sudoriparas, aparatos respiratorio, digestivo y reproductor, siendo la afectacion de las vias respiratorias la principal causa de morbi-mortalidad. La frecuencia de aparicion de neumotorax va aumentando con la edad del paciente, siendo la edad media de presentacion de 21,9 anos. El principal factor de riesgo para la produccion de neumotorax es la obstruccion bronquial, originandose el 75% de los neumotorax en pacientes con un FEV 1 menor del 40%. Entre otros factores que aumentan la probabilidad de padecer un neumotorax se han descrito: la colonizacion cronica por Pseudomonas aeruginosa, Burkholderia cepacia y Aspergillus , la aspergilosis broncopulmonar alergica (ABPA), el recibir alimentacion enteral por desnutricion, la hemoptisis masiva, la insuficiencia pancreatica y la terapia con tobramicina o DNasa inhalada. Presentamos el caso de un paciente que ha sufrido 10 neumotorax en el transcurso de un ano.

Los Actinomyces son bacterias anaerobias, que crecen formando racimos y filamentos y forman parte de la flora normal de la orofaringe, tracto gastrointestinal y genital femenino. Existen catorce especies de Actinomyces , siendo A . israeli la principal especie patogena en humanos. La mayoria de dichas infecciones son polimicrobianas, como en el caso que presentamos a continuacion de una paciente con neumonia polimicrobiana y absceso cutaneo.

Background A very weak relationship has been reported between the health-related quality of life (HRQL) of patients with asthma and their degree of airway hyper-responsiveness (AHR), evaluated in terms of sensitivity. However, this relationship still has not been sufficiently explored for bronchial reactivity indices. Objectives To analyse the relationship between bronchial reactivity and sensitivity with the HRQL of patients with stable asthma, identifying the functional parameters that determine HRQL. Methods In 103 consecutive patients with stable asthma, HRQL was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). Patients underwent spirometry and non-specific bronchial provocation with methacoline. Sensitivity (PD20) and reactivity (dose–response slope (DRS), continuous index of responsiveness (CIR) and bronchial reactivity index (BRI)) of the dose–response curve were analysed. Results BRI presented significant differences with different degrees of asthma severity. Although patients with AHR showed poorer quality of life than patients without AHR, the AQLQ total score was not related to PD20 but rather to DRS (r=−0.784), CIR (r=−0.712) and BRI (r=−0.776). The indices of bronchial reactivity reached a negative correlation with all the domains of the AQLQ. In a multiple linear regression model, BRI, DRS, FIV1 (forced inspiratory volume in 1 s) and VCIN (inspiratory vital capacity) were identified as independent predictors of the AQLQ total score (r2=0.742, p

215 Adherence with TOBI® among cystic fibrosis patients with Pseudomonas aeruginosa infection V.N. Joish1, S.S. Sansgiry2, S.H. Boklage1, P.A. Chopra2, S. Sethi3. 1Bayer Healthcare Pharmaceuticals Inc., Health Economics and Outcomes Research, Wayne, United States; 2University of Houston, Clinical Sciences and Administration, Houston, United States; 3University at Buffalo, State University of New York, Buffalo, United States

Introduction: A20 is a negative regulator of TLR driven NF-uB signalling. This regulatory function is reliant on the formation of a ubiquitin editing complex comprising A20, Ring Finger protein (RNF)11, Itch (E3 ligase) and the adaptor protein TAX1BP1 [1]. In CF epithelial cells LPS reduces the expression of all complex members. Moreover, A20 does not interact with other complex members or target proteins [2,3]. Here we sought to determine the role of CFTR in the down-regulation of A20 ubiquitin editing genes. Methods: 16HBE41obronchial epithelial cells were transfected with CFTR siRNA. Primary nasal epithelial cells (NECs) from CF patients [F508del homozygous (n = 6), or R117H/F508del heterozygous (n = 5)] and age-matched controls (n = 6) were fully differentiated at air-liquid interface and treated with LPS (P. aeruginosa, Sigma) for 24h. A20, RNF11, Itch and TAX1BP1 mRNA expression was assessed by qPCR and analysed by ANOVA. Results: Following CFTR knockdown (transfection efficiency 72%±5.34%, n = 3) A20 mRNA was reduced by 43% (P < 0.01). This would indicate that A20 expression may be regulated by CFTR. In line with this, expression of A20, RNF11, Itch and TAX1BP1 was significantly reduced (P < 0.01–0.001) in NECs from both CF groups compared with controls. Moreover, the reduction in A20, RNF11 and TAX1BP1 (P < 0.05) expression was more pronounced in the F508del than R117H group. Conclusion: Expression of the A20 ubiquitin editing complex reflects CF disease severity and may prove a novel predictor of inflammation. The CF Trust UK (PJ541) supported this work