Cohort profile: the Hortega Study for the evaluation of non-traditional risk factors of cardiometabolic and other chronic diseases in a general population from Spain.

PURPOSE: The Hortega Study is a prospective study, which investigates novel determinants of selected chronic conditions with an emphasis on cardiovascular health in a representative sample of a general population from Spain. PARTICIPANTS: In 1997, a mailed survey was sent to a random selection of public health system beneficiaries assigned to the University Hospital Rio Hortega's catchment area in Valladolid (Spain) (n=11 423, phase I), followed by a pilot examination in 1999-2000 of 495 phase I participants (phase II). In 2001-2003, the examination of 1502 individuals constituted the Hortega Study baseline examination visit (phase III, mean age 48.7 years, 49% men, 17% with obesity, 27% current smokers). Follow-up of phase III participants (also termed Hortega Follow-up Study) was obtained as of 30 November 2015 through review of health records (9.5% of participants without follow-up information). FINDINGS TO DATE: The Hortega Study integrates baseline information of traditional and non-traditional factors (metabolomic including lipidomic and oxidative stress metabolites, genetic variants and environmental factors, such as metals), with 14 years of follow-up for the assessment of mortality and incidence of chronic diseases. Preliminary analysis of time to event data shows that well-known cardiovascular risk factors are associated with cardiovascular incidence rates, which add robustness to our cohort. FUTURE PLANS: In 2020, we will review updated health and mortality records of this ongoing cohort for a 5-year follow-up extension. We will also re-examine elder survivors to evaluate specific aspects of ageing and conduct geolocation to study additional environmental exposures. Stored biological specimens are available for analysis of new biomarkers. The Hortega Study will, thus, enable the identification of novel factors based on time to event data, potentially contributing to the prevention and control of chronic diseases in ageing populations.

Implicación de los servicios de neumología españoles en la asistencia, docencia e investigación en asma. Resultados de la encuesta ATENEA / Involvement of Spanish Pulmonology Centers in Patient Care, Postgraduate Education and Research in Asthma: The Results of the ATENEA Survey

Si bien el asma es una de las enfermedades respiratorias crónicas más prevalentes, existe la sospecha de que la participación de los centros de neumología españoles en su manejo es potencialmente mejorable. Objetivo: Determinar el grado de implicación de los servicios de neumología españoles en la asistencia, docencia e investigación relacionadas con la enfermedad asmática y específicamente con la de control difícil. Método: Se remitió una encuesta formada por 75 ítems que cumplimentaron los responsables de los centros entrevistados. La encuesta interrogaba sobre la asistencia neumológica general y la del asma en particular, así como la actividad docente e investigadora en la enfermedad asmática en los cinco años previos. Resultados: De las 107 encuestas enviadas, 69 (64,5%) centros las retornaron cumplimentadas. De estos, 47 (68,1%) reunieron criterios de actividad asistencial destacada en asma. Sin embargo, solo 29 (42%) disponían de una consulta monográfica de asma de control difícil y 37 (53,6%) utilizaban un programa de educación. En el ámbito docente, únicamente 31 (44,9%) proporcionaban formación específica sobre asma a sus médicos residentes. Y en el de investigación, 12 (17,4%) referían tener proyectos subvencionados por SEPAR y 25 (36,2%) habían publicado trabajos en revistas con factor de impacto. Conclusiones: Si bien la mayoría de los centros neumológicos entrevistados refieren una notable actividad en la asistencia del asma, su implicación en el abordaje especializado del asma de control difícil es insuficiente. Así mismo, su participación en actividades docentes y de investigación relacionadas con la enfermedad es desigual y limitada a escasos centros(AU)

Although asthma is one of the most prevalent chronic respiratory diseases, the participation of Spanish pulmonology units in the management of asthma may have room for improvement. Objective: To determine the degree of involvement of the Spanish pulmonology services in the patient care, education and research related with asthma disease and especially in difficult-to-control asthma. Methods: A survey made up of 75 questions was sent to the heads of several pulmonology departments. The survey asked questions pertaining to respiratory disease care in general, and in asthma in particular, as well as the educational activities and research in asthma during the previous five years. Results: Out of the 107 surveys sent, 69 (645%) centers filled them out and returned them. Forty-seven (681%) met the criteria for an important level of health-care activity in asthma. However, only 29 (42%) had a monographic consultation for difficult-to-control asthma and 37 (536%) used an education program. As for postgraduate education, only 31 (449%) provided their resident physicians with specific asthma training. And in the research field, 12 (174%) reported having projects funded by SEPAR and 25 (362%) had published studies in journals with an impact factor. Conclusions: Although the majority of the pulmonology centers interviewed report a notable activity in asthma patient care, their involvement in the specialized approach for difficult-to-control asthma is insufficient. Likewise, participation in educational activities and research related with the disease is inconsistent and limited to few centers(AU)

Involvement of Spanish pulmonology centers in patient care, postgraduate education and research in asthma: the results of the ATENEA survey.

UNLABELLED: Although asthma is one of the most prevalent chronic respiratory diseases, the participation of Spanish pulmonology units in the management of asthma may have room for improvement. OBJECTIVE: To determine the degree of involvement of the Spanish pulmonology services in the patient care, education and research related with asthma disease and especially in difficult-to-control asthma. METHODS: A survey made up of 75 questions was sent to the heads of several pulmonology departments. The survey asked questions pertaining to respiratory disease care in general, and in asthma in particular, as well as the educational activities and research in asthma during the previous five years. RESULTS: Out of the 107 surveys sent, 69 (645%) centers filled them out and returned them. Forty-seven (681%) met the criteria for an important level of health-care activity in asthma. However, only 29 (42%) had a monographic consultation for difficult-to-control asthma and 37 (536%) used an education program. As for postgraduate education, only 31 (449%) provided their resident physicians with specific asthma training. And in the research field, 12 (174%) reported having projects funded by SEPAR and 25 (362%) had published studies in journals with an impact factor. CONCLUSIONS: Although the majority of the pulmonology centers interviewed report a notable activity in asthma patient care, their involvement in the specialized approach for difficult-to-control asthma is insufficient. Likewise, participation in educational activities and research related with the disease is inconsistent and limited to few centers.

Flow cytometry analysis of leukocytes in induced sputum from asthmatic patients.

Inflammatory cell counts in induced sputum from asthmatic patients partially correlate with respiratory physiology data. To identify and quantify these inflammatory components, microscopy has been useful but it is not without its limitations. Flow cytometry could be an alternative but still has underlying methodological difficulties. While passing airways, leukocytes undergo morphologic cellular changes that alter their conventional phenotype. To demonstrate the usefulness of cytometry in accurately identifying cellular profiles in induced sputum of asthmatic and chronic cough patients, we introduced a new panel of monoclonal antibodies against specific subset markers. To identify neutrophils, sputum cells were stained with CD45 and CD66b. To identify eosinophils, sputum cells were stained with anti-CD45 and anti-CD125. We co-stained CD45, CD14 and CD66b to identify macrophages as CD45+CD14+CD66b- cells. Comparable results of trypan blue exclusion and annexin V-FITC suggested that cytometry manipulation did not decrease cellular viability. Range values were similar in microscopy neutrophils (median 19.9%, range 1.7-90.1%) and CD45+CD66b+ neutrophils (median 31% range 0.9-89%). After gating out CD45- non-leukocyte events, CD45+ and SSC dot-plots defined three patterns of leukocyte distribution. The eosinophil range in microscopic examination was 0-71.3% (median 2.85%) whereas CD45+CD125+ cell range in cytometry was 0-29% (median 3.7%). Since no exclusive markers were found on airways macrophages, we co-stained CD45, CD14 and CD66b to identify macrophages as CD45+CD14+CD66b- cells. Microscopy showed that macrophage and CD45+CD14+CD66b- cell counts were comparable (median 52.3 and range 6.7-94.8 vs median 61 and range 10.5-97.7 respectively). Correlations between neutrophils, eosinophils and macrophages in microscopic examination and flow cytometry were strong (R=0.725, 0.747 and 0.532, respectively p<0.001). This study validates effectiveness of combining specific antibodies and cytometry to quantify inflammatory leukocytes in induced sputum. Multiple markers at a single cell level will deepen our knowledge concerning the phenotype of airway leukocytes.

Pulmonary function testing prior to reduced intensity conditioning allogeneic stem cell transplantation in an unselected patient cohort predicts posttransplantation pulmonary complications and outcome.

Pretransplant pulmonary function tests (PFTs) have been checked mostly in myeloablative allogeneic stem cell transplantation (Allo-SCT). Their value in the setting of reduced intensity conditioning Allo-SCT (Allo-RIC) has been less explored. We retrospectively evaluated the predictive value of PFTs on posttransplant pulmonary complications (PPC) and outcomes in 195 consecutive Allo-RIC patients, based on fludarabine plus busulphan or melphalan. PFT parameters included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, total lung capacity (TLC), residual volume, and diffusion capacity for carbon monoxide (DLCo) corrected for the hemoglobin levels. Pretransplant PFTs abnormalities were observed in 130 patients (66%). The most frequent abnormalities were abnormal DLCO (n = 83, 44%), followed by FEV1/FVC (n = 75, 38%) and FVC (n = 47, 24%). The abnormalities were severe in 25 (13%) patients, moderate in 65 (33%) and mild in 40 patients (21%). Multivariate analysis showed that TLC was significantly associated with PPC, nonrelapse mortality and overall survival (OS), (HR 4.2, 95% CI. 2-8.5; HR 3.8, 95% CI. 1.7-8.5; HR 2.3, 95% CI. 1.3-4.1, respectively, P = 0.01), while abnormal FVC had a negative impact on PPC and OS (HR 1.8, 95% CI. 0.98-3.6, P = 0.06 and HR 1.7, 95% CI. 1.1-2.6, P = 0.008). This study emphasizes the valuable role of PFTs in identifying patients at risk for PPC, NRM, and lower OS in the Allo-RIC setting.

Inflamación bronquial, clínica respiratoria y función pulmonar en el síndrome de Sjögren primario / Bronchial Inflammation, Respiratory Symptoms and Lung Function in Primary Sjögren’s Syndrome

Introducción: En el síndrome de Sjögren primario (SSp) no se dispone de información suficiente queanalice la relación entre la clínica respiratoria o la función pulmonar y la inflamación bronquial presente,medida por esputo inducido.Objetivo: Descripción de las características clínicas y de función pulmonar en los pacientes diagnosticadosde SSp y su relación con el perfil inflamatorio de la luz bronquial.Métodos: Se analizaron síntomas respiratorios, radiología, función pulmonar, hiperrespuesta bronquiale inflamación mediante esputo inducido de 36 pacientes consecutivos diagnosticados de SSp.Resultados: El 58% de los pacientes presentó carraspera y el 42% tos y disnea. No hubo alteraciones destacablesde la función pulmonar, pero el 46% (n = 16) presentó una prueba de respuesta bronquial positiva.La linfocitosis > 2,6% en esputo estaba presente en el 69% de los esputos analizados. Presentaron toscrónica el 29% de los pacientes con linfocitosis (n = 24), frente al 73% de los normales (n = 11) (p = 0,02),con una duración de la tos inferior para el primero (p = 0,02). Por el contrario, la hiperrespuesta bronquialse asoció con linfocitosis (p = 0,02). El 55% de los esputos patológicos (n = 22) presentaron lipófagos(índice > 15) frente al 18% de los normales (n = 11) (p = 0,05).Conclusión: Los síntomas respiratorios (carraspera, tos y disnea) son frecuentes en el SSp aunque surelación con la hiperrespuesta bronquial y la inflamación de la vía aérea es variable. El hallazgo de linfocitosisen la vía aérea constituye un foco infiltrativo más de la enfermedad, siendo el esputo inducidouna herramienta complementaria en la valoración de la actividad inflamatoria pulmonar del SSp(AU)

Introduction: There is no information available regarding the relationship between the respiratory symptomsor lung function and bronchial inflammation, measured by induced sputum.Objectives: Description of the clinical characteristics, radiographic images and lung function of patientssuffering from Primary Sjögren Syndrome (PSS), and to assess the relationship with the inflammatoryairway profile.Methods: Weanalysed clinical, radiology, lung function tests, bronchial hyperresponsiveness and inflammatorydata in the induced sputum from 36 consecutive patients with PSS.Results: A total of 58% of patients had hoarseness and 42% had cough and dispnea. No lung dysfunctionwas observed, although 46% (n = 16) had a positive bronchial response. Lymphocytosis >2.6% in inducedsputum was observed in 69% of all sputa. There was chronic coughin 29% of patients with lymphocytosis(n = 24), whereas 73% were normal (n = 11) (P = .02). The duration time of cough was less for the former (P = .02). On the contrary a positive bronchial response was associated with lymphocytosis >2.6% (P = .02). Lipophages were presnt in 55% of pathological sputa (n = 22) (index >15) versus 18% of the non-pathological ones (n = 11) (P = .05). Conclusion: Hoarseness, cough and dyspnea are frequent respiratory symptoms in PSS, although there is awide variation in the relationship with bronchial responsiveness and airway inflammation. Lymphocytosisin the airways is another site of the infiltrative process in PSS, and the induced sputum is a complementarytool in the identification of active inflammatory process(AU)

Bronchial inflammation, respiratory symptoms and lung function in Primary Sjögren's syndrome.

INTRODUCTION: There is no information available regarding the relationship between the respiratory symptoms or lung function and bronchial inflammation, measured by induced sputum. OBJECTIVES: Description of the clinical characteristics, radiographic images and lung function of patients suffering from Primary Sjögren Syndrome (PSS), and to assess the relationship with the inflammatory airway profile. METHODS: We analysed clinical, radiology, lung function tests, bronchial hyperresponsiveness and inflammatory data in the induced sputum from 36 consecutive patients with PSS. RESULTS: A total of 58% of patients had hoarseness and 42% had cough and dispnea. No lung dysfunction was observed, although 46% (n=16) had a positive bronchial response. Lymphocytosis >2.6% in induced sputum was observed in 69% of all sputa. There was chronic cough in 29% of patients with lymphocytosis (n=24), whereas 73% were normal (n=11) (P=.02). The duration time of cough was less for the former (P=.02). On the contrary a positive bronchial response was associated with lymphocytosis >2.6% (P=.02). Lipophages were present in 55% of pathological sputa (n=22) (index >15) versus 18% of the non-pathological ones (n=11) (P=.05). CONCLUSION: Hoarseness, cough and dyspnea are frequent respiratory symptoms in PSS, although there is a wide variation in the relationship with bronchial responsiveness and airway inflammation. Lymphocytosis in the airways is another site of the infiltrative process in PSS, and the induced sputum is a complementary tool in the identification of active inflammatory process.

Respuesta inflamatoria de la exacerbación asmática de instauración rápida / Inflammatory Response of Rapid Onset Asthma Exacerbation

No se ha estudiado suficientemente la asociación entre la rapidez de instauración de la crisis de asma y la respuesta inflamatoria desencadenada.ObjetivoDeterminar los mecanismos inflamatorios que caracterizan la exacerbación asmática de instauración rápida.MétodoSe diseñó un estudio prospectivo y multicéntrico en los servicios de urgencias hospitalarias, que evaluó a 34 pacientes que se distribuyeron en tres grupos en función de las horas de instauración de la exacerbación asmática: (menos de 24h), instauración intermedia (25–144h), e instauración lenta (145 o más horas). Se recogieron datos clínicos, de esputo, sangre y orina en el momento de la primera atención y pasadas 24h, determinándose celularidad inflamatoria y marcadores solubles.ResultadosLos pacientes con exacerbación rápida presentaron una significativa mayor concentración de elastasa (1.028±1.140; 310±364; 401±390ng/ml) y albúmina (46,2± 4,3; 42±3,4; 39,9±4,8g/l) en sangre. El número de neutrófilos, eosinófilos, (tanto en sangre como en esputo), los niveles de proteína catiónica del eosinófilo (PCE) (sangre), interleuquina 8 (IL8) (sangre) y leucotrieno E4 (LTE4) (orina) estaban elevadas en los tres grupos (p>0,05). Se constataron asociaciones lineales entre el tiempo de instauración de la exacerbación y la intensidad de la obstrucción (FEV1) (r=−0,360; p=0,037), los eosinófilos en esputo (r=−0,399; p=0,029), la albúmina (r=−0,442; p=0,013); y con la IL8 (r=0,357; p=0,038).ConclusionesLos resultados sugieren una activación precoz de la respuesta neutrofílica y eosinofílica en la exacerbación asmática. No obstante, es posible que el edema bronquial juegue un papel importante en la respuesta inicial inflamatoria de las exacerbaciones dependiendo del tiempo de instauración(AU)

The association between onset of asthma exacerbation and the inflammatory response has not been sufficiently studied.ObjectiveTo determine the differential mechanisms of the rapid onset (RO) asthma exacerbation.MethodsWe designed a prospective, multicentre study that included 34 patients who suffered from asthma exacerbation. They were distributed into three groups of asthmatics, depending of the time of onset: from 0 to 24h, from 25 to 144h and more than 145h. We collected clinical data, sputum, blood and urine samples when first seen at the clinic and the next 24h later, and differential cell counts and biomarkers were determinedResultsThe asthmatics who suffered a RO exacerbation showed a higher elastase concentration, (1.028±1.140; 310±364; 401±390ng/ml) (P<0.05) and albumin (46.2±4.3; 42±3.4; 39.9±4.8g/l) (P<0.05) in the blood sample. Neutrophils, eosinophils (blood or sputum), eosinophil cationic protein (ECP) (blood), interleukin 8 (IL8) (blood) and leukotriene E4 (LTE4) (urine) were high in the three groups (P>0.05). We demonstrated an association between the onset of exacerbation and the severity of obstruction (FEV1) (r=−0.360; P=0.037), eosinophils in sputum (r=−0.399; P=0.029), albumin (r=−0.442; P=0.013), and IL8 in sputum (r=0.357; P=0.038).ConclusionsThe results suggest a rapid inflammatory response, both neutrophilic and eosinophilic, in the asthmatic exacerbation. However, the swelling in the bronchi may play an important role in the initial inflammatory response in the exacerbations depending of time of onset(AU)

[Inflammatory response of rapid onset asthma exacerbation]. / Respuesta inflamatoria de la exacerbación asmática de instauración rápida.

UNLABELLED: The association between onset of asthma exacerbation and the inflammatory response has not been sufficiently studied. OBJECTIVE: To determine the differential mechanisms of the rapid onset (RO) asthma exacerbation. METHODS: We designed a prospective, multicentre study that included 34 patients who suffered from asthma exacerbation. They were distributed into three groups of asthmatics, depending of the time of onset: from 0 to 24h, from 25 to 144h and more than 145h. We collected clinical data, sputum, blood and urine samples when first seen at the clinic and the next 24h later, and differential cell counts and biomarkers were determined RESULTS: The asthmatics who suffered a RO exacerbation showed a higher elastase concentration, (1.028±1.140; 310±364; 401±390ng/ml) (P<0.05) and albumin (46.2±4.3; 42±3.4; 39.9±4.8g/l) (P<0.05) in the blood sample. Neutrophils, eosinophils (blood or sputum), eosinophil cationic protein (ECP) (blood), interleukin 8 (IL(8)) (blood) and leukotriene E4 (LTE(4)) (urine) were high in the three groups (P>0.05). We demonstrated an association between the onset of exacerbation and the severity of obstruction (FEV(1)) (r=-0.360; P=0.037), eosinophils in sputum (r=-0.399; P=0.029), albumin (r=-0.442; P=0.013), and IL(8) in sputum (r=0.357; P=0.038). CONCLUSIONS: The results suggest a rapid inflammatory response, both neutrophilic and eosinophilic, in the asthmatic exacerbation. However, the swelling in the bronchi may play an important role in the initial inflammatory response in the exacerbations depending of time of onset.

Impacto del tratamiento preventivo con agonistas adrenérgicos B2 de acción larga y glucocorticoides inhalados en la morbimortalidad de 1.543 episodios de exacerbación grave de asma / Impact of Preventive Treatment With Long-Acting B2-Adrenergic Agonists and Inhaled Corticosteroids on the Morbidity and Mortality of Severe Asthma Exacerbations in 1543 Patients

IntroducciónRecientes revisiones sistemáticas y metaanálisis que han analizado la seguridad de los agonistas adrenérgicos β2 de acción larga por vía inhalada en el tratamiento de mantenimiento del asma han mostrado, sorprendentemente, resultados dispares. El objetivo de este estudio ha sido analizar el impacto, en términos de eficacia y seguridad, del tratamiento previo de mantenimiento del asma en la exacerbación asmática grave.Pacientes y métodosSe han evaluado retrospectivamente las características clínicas de las exacerbaciones graves que presentaron 1.543 pacientes con asma persistente moderada o grave, de los que 493 recibían previamente un agonista adrenérgico β2 de acción larga más un glucocorticoide, ambos inhalados; 456 recibían sólo un glucocorticoide inhalado, y 594 no seguían ningún tratamiento de mantenimiento.ResultadosEl grupo que recibía un agonista adrenérgico β2 de acción larga inhalado no presentó mayores mortalidad, necesidad de ingreso en la unidad de cuidados intensivos y estancia hospitalaria, peor pH ni mayor obstrucción del flujo aéreo que los otros 2 grupos de pacientes. Por el contrario, al recibir el alta hospitalaria presentó un volumen espiratorio forzado en el primer segundo significativamente mejor (p=0,009): media±desviación estándar del 54±16%, frente al 48±19 y el 48±20% de los otros 2 grupos. En el grupo que no recibía tratamiento previo el pH fue significativamente peor (7,37±0,11, frente a 7,39±0,09 y 7,39±0,08) y hubo una mayor proporción de pacientes que precisaron ingreso en la unidad de cuidados intensivos (el 11,1 frente al 6,5 y el 7,7%), en comparación con los otros 2 (p=0,002 y p=0,018, respectivamente)(AU)

ConclusionesEl presente estudio no constató una mayor morbimortalidad de la exacerbación asmática grave en los pacientes con asma persistente moderada-grave que recibían previamente tratamiento con un agonista adrenérgico β2 de acción larga y un glucocorticoide inhalados. Por el contrario, quienes no seguían tratamiento de mantenimiento presentaron una exacerbación más grave(AU)

Background and ObjectivesRecent systematic reviews and meta-analyses examining long-acting #b2-adrenergic agonists (LABA) as maintenance treatment for asthma have shown surprisingly conflicting results. The aim of the present study was to determine the impact, in terms of efficacy and safety, of previous maintenance treatment on severe asthma exacerbations.Patients and MethodsWe retrospectively evaluated the clinical characteristics of exacerbations experienced by 1543 patients with moderate persistent and severe persistent asthma. Drug therapy was as follows: a combination of inhaled LABAs and corticosteroids (493 patients), an inhaled corticosteroid only (456 patients), and no maintenance treatment (594 patients).ResultsAsthmatic patients taking LABAs did not show higher mortality, longer stay in the intensive care unit, longer hospital stay, lower pH, or worse airflow obstruction than the other 2 groups. On the contrary, they had a higher mean (SD) forced expiratory volume in 1 second at discharge (54% [16%]) than patients taking inhaled corticosteroids (48% [19%]) and patients taking no maintenance treatment (48% [20%]) (P=.009). Patients taking no maintenance treatment also had lower mean (SD) pH values (7.37 [0.11]) than patients taking LABAs (7.39 [0.09]) and patients taking inhaled corticosteroids (7.39 [0.08]) (P=.002), and more admissions to the intensive care unit (11.1% vs 6.5% and 7.7%; P=.002 and P=.018, respectively).ConclusionsThis study did not reveal higher morbidity or mortality in severe asthma exacerbations in patients with moderate persistent or severe persistent asthma who had received inhaled LABAs combined with inhaled corticosteroids. On the contrary, asthma patients who did not use maintenance treatment experienced more severe asthma exacerbations(AU)

The study of severe asthma in Latin America and Spain (1994-2004): characteristics of patients hospitalized with acute severe asthma.

OBJECTIVE: Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. METHODS: This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. RESULTS: Over time, the use of inhaled corticosteroids and long-acting beta2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. CONCLUSIONS: Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.

[Impact of preventive treatment with long-acting beta(2)-adrenergic agonists and inhaled corticosteroids on the morbidity and mortality of severe asthma exacerbations in 1543 patients]. / Impacto del tratamiento preventivo con agonistas adrenérgicos beta(2) de acción larga y glucocorticoides inhalados en la morbimortalidad de 1.543 episodios de exacerbación grave de asma.

BACKGROUND AND OBJECTIVES: Recent systematic reviews and meta-analyses examining long-acting #b(2)-adrenergic agonists (LABA) as maintenance treatment for asthma have shown surprisingly conflicting results. The aim of the present study was to determine the impact, in terms of efficacy and safety, of previous maintenance treatment on severe asthma exacerbations. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics of exacerbations experienced by 1543 patients with moderate persistent and severe persistent asthma. Drug therapy was as follows: a combination of inhaled LABAs and corticosteroids (493 patients), an inhaled corticosteroid only (456 patients), and no maintenance treatment (594 patients). RESULTS: Asthmatic patients taking LABAs did not show higher mortality, longer stay in the intensive care unit, longer hospital stay, lower pH, or worse airflow obstruction than the other 2 groups. On the contrary, they had a higher mean (SD) forced expiratory volume in 1 second at discharge (54% [16%]) than patients taking inhaled corticosteroids (48% [19%]) and patients taking no maintenance treatment (48% [20%]) (P=.009). Patients taking no maintenance treatment also had lower mean (SD) pH values (7.37 [0.11]) than patients taking LABAs (7.39 [0.09]) and patients taking inhaled corticosteroids (7.39 [0.08]) (P=.002), and more admissions to the intensive care unit (11.1% vs 6.5% and 7.7%; P=.002 and P=.018, respectively). CONCLUSIONS: This study did not reveal higher morbidity or mortality in severe asthma exacerbations in patients with moderate persistent or severe persistent asthma who had received inhaled LABAs combined with inhaled corticosteroids. On the contrary, asthma patients who did not use maintenance treatment experienced more severe asthma exacerbations.

The study of severe asthma in Latin America and Spain (1994-2004): characteristics of patients hospitalized with acute severe asthma / Estudo sobre Asma Grave na América Latina e Espanha (1994-2004): características dos pacientes hospitalizados com asma aguda grave

Objective: Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. Methods: This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. Results: Over time, the use of inhaled corticosteroids and long-acting β2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. Conclusions: Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.

Objetivo: Estudos que avaliem as características e o gerenciamento de pacientes asmáticos hospitalizados têm sido limitados a um número pequeno de serviços e a curtos períodos de duração. O presente estudo avaliou alteraçõesde longo prazo de pacientes asmáticos hospitalizados em um grande número de serviços. Métodos: Estudo retrospectivo,observacional, de base hospitalar, denominado Estudo sobre Asma Grave na América Latina e Espanha, realizado na Espanha e em oito países da América Latina. Foi realizada uma revisão dos registros hospitalares de 3.038 pacientes (variação de idade, 15-69 anos) hospitalizados com asma aguda grave em um dos 19 hospitais terciários em 1994, 1999 e 2004. Resultados: Ao longo do tempo, o uso de corticosteroides inalatórios e de β2-agonistas aumentou significativamente, ao passo que o uso de teofilina, como medicação de controle, decaiu. A utilização de testes de função pulmonar também aumentou. Houve uma redução significativa da média do tempo de internação (8,5 dias, 7,4 dias e 7,1 dias em 1994, 1999 e 2004, respectivamente; p = 0,0001) e um aumento significativo da média do menor pH arterial na admissão. Em contrapartida, houve uma diminuição significativa na proporção de casos submetidos ao PFE no pronto-socorro (48,6% em 1994 vs. 43,5% em 2004; p = 0,0001). O tratamento e o gerenciamento da asma foram, de forma geral, melhores na Espanha que na América Latina. Conclusões: Embora tenha havido avanços no gerenciamento da asma entre exacerbações graves e durante a hospitalização, esse gerenciamento continua subotimizado na Espanha e, em especial, na América Latina.

[Asthma clinical practice guidelines: advantages and pitfalls]. / Guías de Práctica Clínica para el asma. Luces y sombras.

The Clinical Practice Guidelines on asthma have contributed towards unifying concepts and reaching a consensus on performances between different professional groups. However, they have failed in the overall improvement in the management of asthma, the final objective that they are meant to achieve. Today, almost 20 years after they appeared, the majority of asthmatic patients are still inadequately controlled, partly due to lack of follow up by doctors and the rest of health care staff who have to look after them. This lack of follow up of these recommendations is probably associated with a lack of well structured planning in their circulation and implementation. Also, although the recommendations of these guidelines agree in what is essential, they differ in other aspects, which in turn could be determining factors in clinical practice. The purpose of this article has been to establish the main differences in the recommendations that the principal clinical practice guidelines on the disease propose on the diagnosis, classification and treatment of asthma. To do this we have compared, The British Guideline on the Management of Asthma 2007, The Global Strategy for Asthma Management and Prevention/Global Initiative for Asthma 2006 (GINA), the National Prevention program for Education on Asthma (Programa Nacional de Prevención para la Educación del Asma) (NAEPP), the Spanish Guide for the Management of Asthma (Guía Española para el Manejo del Asma 2003) (GEMA) and the ALAT y SEPAR guides, Latin-America and Spain. Recommendations for the Prevention and Treatment of Asthma Exacerbation (América Latina y España. Recomendaciones para la Prevención y el Tratamiento de la Exacerbación Asmática 2008) (ALERTA).

Guías de Práctica Clínica para el asma. Luces y sombras / Asthma Clinical Practice Guidelines: Advantages and Pitfalls

Las guías de práctica clínica sobre asma han contribuido a unificar conceptos y consensuar actuacionesentre grupos dispares de profesionales. Sin embargo, han fracasado en la mejora global del manejo delasma, objetivo último que persiguen. Todavía hoy, casi 20 años después de su aparición, la mayoría de lospacientes asmáticos continúa insuficientemente controlado, en parte debido a su escaso seguimiento porlos médicos y el resto del personal sanitario que los debe atender. Esta falta de seguimiento de esas recomendacionesprobablemente esté relacionada con la falta de una planificación bien estructurada en su difusióne implementación. Además, si bien las recomendaciones de esas guías coinciden en lo esencial,difieren en otros aspectos, que luego podrían ser determinantes en la práctica clínica.El objetivo del presente artículo ha sido constatar las principales diferencias en las recomendaciones quesobre el diagnóstico, la clasificación y el tratamiento del asma proponen las principales guías de prácticaclínica sobre la enfermedad. Para ello se han comparado The British Guideline on the Management of Asthma2007, The Global Strategy for Asthma Management and Prevention/Global Initiative for Asthma 2006(GINA), el Programa Nacional de Prevención para la Educación del Asma (NAEPP), la Guía Española para elManejo del Asma 2003 (GEMA) y la guía de ALAT y SEPAR, América Latina y España. Recomendaciones parala Prevención y el Tratamiento de la Exacerbación Asmática 2008 (ALERTA)(AU)

The Clinical Practice Guidelines on asthma have contributed towards unifying concepts and reaching aconsensus on performances between different professional groups. However, they have failed in the overallimprovement in the management of asthma, the final objective that they are meant to achieve. Today,almost 20 years after they appeared, the majority of asthmatic patients are still inadequately controlled,partly due to lack of follow up by doctors and the rest of health care staff who have to look after them. Thislack of follow up of these recommendations is probably associated with a lack of well structured planningin their circulation and implementation. Also, although the recommendations of these guidelines agree inwhat is essential, they differ in other aspects, which in turn could be determining factors in clinicalpractice.The purpose of this article has been to establish the main differences in the recommendations that theprincipal clinical practice guidelines on the disease propose on the diagnosis, classification and treatmentof asthma. To do this we have compared, The British Guideline on the Management of Asthma 2007, TheGlobal Strategy for Asthma Management and Prevention/Global Initiative for Asthma 2006 (GINA), theNational Prevention program for Education on Asthma (Programa Nacional de Prevención para la Educacióndel Asma) (NAEPP), the Spanish Guide for the Management of Asthma (Guía Española para el Manejo delAsma 2003) (GEMA) and the ALAT y SEPAR guides, Latin-America and Spain. Recommendations for thePrevention and Treatment of Asthma Exacerbation (América Latina y España. Recomendaciones para laPrevención y el Tratamiento de la Exacerbación Asmática 2008) (ALERTA)(AU)

Consideraciones sobre el uso del cuestionario SF-36 en la medida de la calidad de vida relacionada con la salud de los fumadores / On the use of the SF-36 questionnaire to measure health-related quality of life in smokers

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[Asthma and smoking: an unfortunate combination]. / Asma y tabaco: una unión inconveniente.

Asthma is an inflammatory disease of the airways in which a key role is played by certain cells and mediators (T-helper 2 cells, mast cells, eosinophils, interleukin 4 and 5). In certain disorders such as irritant-induced asthma, reactive airways dysfunction syndrome, and asthma due to toluene diisocyanate, inflammation is mediated predominantly by T-helper 1 cells, macrophages and neutrophils. Smoking also produces bronchial inflammation, in this case mediated primarily by macrophages and neutrophils although eosinophil predominance has also been observed in some smokers (an allergic response to certain antigens). The remodeling of the airway wall that accompanies the chronic inflammatory cascade may alter the cell response profile making it difficult to determine which type of inflammatory infiltrate is predominant. The association of asthma and smoking is a reality in our society, and it is a combination that substantially modifies pathogenic mechanisms and gives rise to a more severe clinical picture. Resistance to some of the pharmacotherapies used routinely in the treatment of asthma (corticosteroids) has also been observed and this has favored the use of other drugs (antileukotrienes). One of the preventative measures that should be used more energetically is to encourage patients to stop smoking, paying particular attention to asthmatic smokers.