Origen celular de micropartículas circulantes en pacientes con enfermedad tromboembólica venosa y cáncer / Celular origin of circulating microparticles in patients with venous thromboembolism and cancer

Las micropartículas (MPs) son unas vesículas extracelulares consideradas potentes efectores celulares. Están presentes en individuos sanos y se encuentran elevadas en estados patológicos como enfermedades inflamatorias, neoplásicas y trombosis. La relación entre enfermedad tromboembólica venosa (ETV) y cáncer está bien establecida. Se piensa que las MPs serían una conexión patogénica entre ambas entidades. De confirmarse, podrían utilizarse como biomarcadores. Nuestro objetivo fue caracterizar las MPs en ambas patologías atendiendo a su origen celular (celular, endotelial, plaquetar, leucocitario y las que exhibían en su superficie mucina 1). También se estudiaron parámetros funcionales como el dímero D (DD) y la P-selectina soluble (sPS). Se consideraron 96 pacientes con ETV idiopática y 85 con neoplasias avanzadas de pulmón, gástrico o páncreas. A todos ellos se les realizó un seguimiento clínico de dos años en el que se excluyeron del estudio aquellos que fueron diagnosticados de cáncer en el grupo de ETV o que desarrollaron trombosis en el grupo de pacientes neoplásicos. Finalmente, se analizaron 82 pacientes con ETV y 68 con cáncer. En nuestros resultados encontramos que las MPs totales y las MPs de origen plaquetar diferenciaban ambos grupos de pacientes. Además, se determinaron cifras significativamente mayores de DD y sPS (p <0,001) en el grupo de ETV. Las diferencias encontradas entre ambos grupos, teniendo en cuenta el origen de las MPs, podrían estar causadas por las características protrombóticas del grupo neoplásico y por el secuestro de las mismas dentro de los coágulos activos en el grupo de ETV

Microparticles (MPs) are extracellular vesicles considered to be powerful cellular effectors. They are present in healthy individuals and are elevated in pathological conditions such as inflammatory and neoplastic diseases, and thrombosis. The relationship between venous thromboembolism (VTE) and cancer has been well established. MPs are thought to be a pathogenic connection between the two entities. If confirmed, they could be used as biomarkers. Our aim was to characterize the MPs in both diseases according to their cellular origin (cellular, endothelial, platelet, leukocyte and those that exhibited mucin 1 on their surface). Functional parameters such as D-dimer (DD) and soluble P-selectin (sPsel) were also studied. 96 patients with idiopathic VTE and 85 with advanced lung, stomach or pancreatic neoplasia were considered. All of them were followed clinically for two years and those who were diagnosed with cancer in the VTE group or those who developed thrombosis in the group of neoplastic patients were excluded from the study. Finally, 82 VTE patients and 68 cancer patients were analyzed. In our results, we found that total MPs and platelet-derived MPs differentiated both patient groups. Additionally, significantly greater numbers of DD and sPsel (p <0.001) were determined in the VTE group. The differences found between both groups, taking into account the origin of the MPs, could be caused by the prothrombotic characteristics of the neoplastic group and their sequestration within active clots in the VTE group

Sindrome de Ortner como causa de disfonía en paciente fumador / Ortner syndrome as the cause of dysphony in smokers

El síndrome de Ortner es una causa rara de parálisis del nervio recurrente laríngeo izquierdo debido a una etiología cardiovascular. Presentamos el caso clínico de un hombre de 70 años con historia de disfonía de un mes y medio de evolución diagnosticado de síndrome de Ortner por aneurisma del cayado aórtico (AU)

Ortner's syndrome is a rare cause of left recurrent laryngeal nerve paralysis due to a cardiovascular aetiology. We present a 70 years old man case with one and a half month history of dysphonia with Ortner’s syndrome caused by aortic arch aneurysm diagnosed (AU)

CYFRA 21-1 as a tool for distant metastasis detection in lung cancer.

BACKGROUND: A study to analyse tumor markers (CEA, CA125, CA15.3, CA19.9, CYFRA 21-1, and NSE) for metastasis detection in lung cancer patients. METHODS: Serum tumor markers from 73 lung cancer patients were measured before they were diagnosed. After lung cancer diagnosis, tumor markers were analyzed for the detection of distant metastases. RESULTS: In NSCLC patients CYFRA 21-1 and NSE showed differences between stage IV and any of the other stages, p < 0.05. The accuracy for metastasis detection was AUC = 81.5 % for CYFRA 21-1 and AUC = 78.6 % for < 0.05) were independent predictors for metastasis presence. No tumor marker showed significant differences according to stages in SCLC patients. CONCLUSIONS: CYFRA 21-1 could be used as a screening tool for metastasis detection in lung cancer patients without symptoms of metastasis as well as CYFRA 21-1 and NSE in NSCLC patients.

[Risk factors for bronchial asthma in patients with rhinitis]. / Factores de riesgo asociados con asma bronquial en pacientes con rinitis.

OBJECTIVES: To identify risk factors for bronchial asthma in a large sample of patients with rhinitis. PATIENTS AND METHODS: One thousand seven hundred sixty patients with rhinitis treated at the respiratory medicine out-patient service of Hospital Universitario Virgen de Rocío in Seville (Spain) in 1997 and 1998 were studied. Six hundred forty-one (36.4%) had isolated rhinitis and 1,119 (63.6%) had rhinitis and bronchial asthma. The following variables were analyzed for both groups: 1) age, 2) sex, 3) clinical diagnosis, 4) age of onset of symptoms, 5) a family history of asthma and/or atopy, 6) housing conditions, 7) smoking, 8) a history of skin allergy, 9) recurrent episodes of respiratory infection with wheezing during early childhood, 10) a diagnosis of nasosinus polyposis, 11) atopy and sensitivity (pollens and/or household allergens), 12) peripheral blood eosinophil count. RESULTS: The variables that best differentiated the group with rhinitis from the group with both rhinitis and asthma were age, family history of asthma and/or atopy, exposure to household humidity or damp, a history of skin allergy, recurrent episodes of respiratory infection with wheezing in early childhood, atopy, sensitivity to household allergens and peripheral blood eosinophil count. The probability of correctly classifying patients in the appropriate group using this model was 69.7%. Among atopic patients, the best predictive variables were the same, with the exception of household humidity/damp. The probability of correct classification using this model was 69.7%. CONCLUSIONS: Patients with rhinitis have risk factors for bronchial asthma. As many such patients as possible should be identified so that long-term follow-up can take place and strategies to prevent bronchial asthma can be implemented.

Factores de riesgo asociados con asma bronquial en pacientes con rinitis / Risk factors for bronchial asthma in patients with rhinitis

OBJETIVOS: Identificar, en una amplia muestra de pacientes con rinitis, aquellos factores asociados con asma bronquial. PACIENTES Y MÉTODOS: Se incluyó en el estudio a 1.760 pacientes diagnosticados de rinitis en nuestras Consultas Externas de Neumología del Hospital Universitario Virgen del Rocío de Sevilla, en un período de 2 años (1997-1998). Seiscientos cuarenta y uno (36,4 por ciento) tenían rinitis aislada y 1.119 (63,6 por ciento) rinitis y asma bronquial. En ambos grupos se analizaron las siguientes variables: edad, sexo, diagnóstico clínico, edad de comienzo de los síntomas, antecedentes familiares de asma y/o atopia, condiciones de la vivienda, hábito tabáquico, antecedentes alérgicos dermatológicos, episodios de infecciones respiratorias con sibilancias recurrentes durante la primera infancia, diagnóstico de poliposis nasosinusal, atopia y tipo de sensibilización (pólenes y/o alergenos domésticos), y porcentaje de eosinófilos en sangre periférica. RESULTADOS: Las mejores variables predictoras para diferenciar el grupo con rinitis del grupo con rinitis y asma fueron la edad, los antecedentes familiares de asma y/o atopia, la exposición a humedad/moho en su vivienda habitual, los antecedentes alérgicos dermatológicos, los episodios de infecciones respiratorias con sibilancias recurrentes en la primera infancia, la atopia, la sensibilización a alergenos domésticos y el porcentaje de eosinófilos en sangre periférica. La probabilidad de clasificar correctamente a los pacientes en cada grupo siguiendo este modelo fue del 69,7 por ciento. Entre los atópicos, las mejores variables predictoras fueron las mismas, exceptuando la exposición a humedad/moho en la vivienda. La probabilidad de clasificación correcta siguiendo este modelo fue del 69,7 por ciento. CONCLUSIONES: En los pacientes riníticos existe una serie de factores de riesgo que van asociados con asma bronquial. Es necesario identificar el mayor número posible de ellos para poder hacer un seguimiento a largo plazo y poner en práctica medidas estratégicas de prevención en aquellos pacientes que presenten más probabilidad de desarrollar asma bronquial (AU)

[Asthma as presentation form of relapsing polychondritis]. / Asma como forma de presentación de policondritis recidivante.

Relapsing polychondritis is a systemic disease of unknown etiology characterised by relapsing inflammation affecting cartilaginous structures, cardiovascular system, eyes and ears. Respiratory involvement occurs in 56% of patients during the disease progression, but only in 14% of cases as an initial presentation. Patients develop severe symptoms due to the disease affecting the glottis and the tracheobronchial tree, which represents the cause of death in 50% of cases. The unspecificity of respiratory symptoms makes that the disease may be confounded with some other if it is not accompanied with a typical presentation, which may cause a delay in the diagnosis. Pulmonary function tests are of great importance, since an obstructive pattern not reversible after bronchodilator administration and a plateau in flow-volume curves are of great help when assessing the severity of the obstruction. High resolution computed tomography is a non-invasive test more precise than bronchoscopy in identifying tracheal and bronchi abnormalities, so it should be performed at the onset of the respiratory symptoms together with the pulmonary function tests. We present the case of a patient, whose disease started with respiratory semiology suggesting bronchial asthma, which preceded in six months the main sign nasal chondritis.

Asma como forma de presentación de policondritis recidivante / Asthma as presentation form of relapsing polychondritis

La policondritis recidivante es una enfermedad sistémica, de etiología desconocida, que se caracteriza por una inflamación recurrente, que afecta a estructuras cartilaginosas, aparato cardiovascular, ojos y oidos. La afectación respiratoria ocurre en el 56 por ciento de los pacientes durante el curso de la enfermedad, pero como forma inicial de presentación sólo ocurre en el 14 por ciento de los casos. Los pacientes desarrollan síntomas severos devidos a la afectación de la glotis y del árbol traqueobronquial, siendo la causa de muerte en el 50 por ciento de los casos. La inespecificidad de los sintomas respiratorios da lugar a que, si el cuadro no se acompaña inicialmente de signos característicos, pueda confundirse con otro proceso, retrasándose el diagnóstico. Las pruebas de función pulmonar son de enorme importancia, apareciendo un patrón obstructivo no reversible tras broncodilatador, y un plateaud en la curva flujo-volumen que va a ayudar a localizar y evaluar la severidad de la obstrucción.La TAC de alta resolución es una exploración no invasiva que identifica las anormalidades de la tráquea y de los bronquios con mas precisión que la broncofibroscopia, por lo que debe realizarse al inicio de los síntomas respiratorios junto con las pruebas de función pulmonar.Presentamos el caso de una paciente cuyo proceso debutó con sintomatología respiratoria sugestiva de asma bronquial, que precedió en seis meses a la aparición del signo guía la condritis nasal. (AU)

[Rhinitis and cough syndrome. Are epidemiologic, clinical and functional characteristics useful in the differential diagnosis with bronchial asthma?]. / Rinitis y síndrome tusígeno. Son de utilidad las características epidemiológicas, clínicas y funcionales en el diagnóstico diferencial con el asma bronquial?

UNLABELLED: Patients often visit family practitioners or respiratory specialists complaining of cough. In non-smokers, the most common cause is postnasal drip secondary to rhinitis. The second most common cause is bronchial asthma. OBJECTIVES: a) To know the epidemiological, clinical and functional features of patients who visit our outpatient pneumology clinic complaining of chronic cough as an isolated symptom, in whom bronchial asthma is suspected, but who have received a diagnosis of rhinitis. b) To analyze the differences between such patients and those in whom chronic cough has been attributed to bronchial asthma. PATIENTS AND METHODS: One hundred thirty-one patients with chronic cough were enrolled for study under the following protocol: 1) taking of a detailed case history (epidemiological and clinical data), 2) physical examination, 3) blood work-up, 4) paranasal sinus and chest X-rays, 5) spirometry at baseline and after 200 micrograms of salbutamol if obstruction was present, 6) methacholine challenge test, 7) skin tests for common respiratory tract allergens, 8) other techniques, depending on suspected diagnosis (CT chest scan, fiberoptic bronchoscopy, consultation with a gastroenterologist or otorhinolaryngologist). RESULTS: One hundred seventeen (89.3%) patients received a diagnosis of rhinitis. Chronic cough was attributed solely to rhinitis in 61 (46.5%) patients. Forty-four (33.5%) were diagnosed as bronchial asthma; 38 (29%) also had rhinitis. Chronic cough was attributed to a different diagnosis in 26 cases (19.8%). The 61 patients with rhinitis as the sole cause of chronic cough were aged 23.8 +/- 10.8 years (9-63 years); 33 (54% of the 61) were men and 28 (46% of the 61) were women. We found that patients with rhinitis more often suffered nasal symptoms (chi 2 = 22.4; p = 0.01), pharyngeal irritation (chi 2 = 9.63, p = 0.05), dry cough from the upper respiratory tract (chi 2 = 16.4, p = 0.001), atopy (chi 2 = 18.1, p < 0.001) and greater FVC (F = 5.28, p = 0.006) than did patients with asthma or other diagnoses. CONCLUSIONS: 1) Rhinitis was the most common cause of chronic cough in the studied patients in whom a diagnosis of bronchial asthma had been suspected. 2) Epidemiological characteristics did not aid differential diagnosis between rhinitis and bronchial asthma (with or without associated rhinitis). 3) A detailed medical history focusing on upper airway symptoms can be useful, although there may be cases of silent postnasal drip syndrome. 4) Paranasal x-rays help to rule out complications of rhinitis. 5) A positive bronchial challenge test does not necessarily indicate a diagnosis of bronchial asthma. 6) Allergy to pollen is the most common finding among atopic patients with rhinitis.

Rinitis y síndrome tusígeno. ¿Son de utilidad las características epidemiológicas, clínicas y funcionales en el diagnóstico diferencial con el asma bronquial? / Rhinitis and chronic cough syndrome: are epidemiological, clinical and functional data useful for ruling out bronchial asthma?

En sujetos no fumadores, la causa más frecuente de tos es el goteo posnasal secundario a rinitis, seguida del asma bronquial. Objetivos: Conocer las características epidemiológicas, clínicas y funcionales de los pacientes con tos crónica como único síntoma, y analizar las diferencias existentes entre el grupo de pacientes que es diagnosticado de rinitis como causa de la tos, y los grupos en los que el síndrome tusígeno se atribuyó a asma bronquial, o a otros diagnósticos. Pacientes y métodos: Se incluyeron 131 pacientes con síndrome tusígeno. El protocolo de estudio fue el siguiente: a) historia clínica detallada (datos epidemiológicos y clínicos); b) exploración física; c) pruebas complementarias: hemograma; radiografías de senos paranasales (nasomentoplaca) y tórax (posteroanterior y lateral); espirometría basal y tras 200 µg de salbutamol si existía obstrucción; prueba de broncoprovocación con metacolina; pruebas alérgicas epicutáneas frente a neumoalergenos habituales; otras técnicas, dependiendo de la sospecha diagnóstica (TAC torácica, fibrobroncoscopia, interconsulta a digestivo u ORL), y d) respuesta al tratamiento. Resultados: Fueron diagnosticados de rinitis 117 pacientes (89,3 por ciento). La tos se atribuyó a rinitis como única causa en 61 pacientes (46,5 por ciento). Cuarenta y cuatro pacientes fueron diagnosticados de asma bronquial (33,5 por ciento) y, de ellos, 38 tenían, además, rinitis (el 29 por ciento del grupo total). En 26 casos (19,8 por ciento) el síndrome tusígeno se atribuyó a otro diagnóstico distinto a los anteriores, y de ellos, 18 pacientes tenían también rinitis asociada (13,7 por ciento). Comparando el grupo en el que la causa del síndrome tusígeno fue la rinitis con los que fueron diagnosticados de asma y con aquellos en los que la tos se atribuyó a otra causa encontramos que el grupo de riníticos tenía con mayor frecuencia sintomatología nasal (*2 = 22,4; p = 0,01); molestias faríngeas (*2 = 9,63; p = 0,05); tos seca de vías altas (*2 = 16,4; p = 0,001); atopia (*2 = 18,1; p < 0,001) y mayor CVF (F = 5,28; p = 0,006). Conclusiones: a) La causa más frecuente de tos crónica en un grupo de pacientes remitidos para su estudio con la sospecha diagnóstica de asma bronquial fue la rinitis; b) las características epidemiológicas no aportaron datos al diagnóstico diferencial entre rinitis y asma bronquial (con o sin rinitis asociada), y sí, las características clínicas; c) la sensibilización a pólenes es la más frecuentemente encontrada entre los sujetos riníticos atópicos, y d) en un paciente, sobre todo joven y no fumador, con síndrome tusígeno, en el que por la historia clínica y la exploración física no se sospecha una causa evidente, estaría indicado hacer un ensayo terapéutico con tratamiento específico para la rinitis. (AU)

[Role of dyspnea in quality of life of the patient with chronic obstructive pulmonary disease]. / Papel de la disnea en la calidad de vida del paciente con enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To analyze the correlation between quality of life and 1) lung function parameters at rest and during exercise, and 2) mean baseline dyspnea measured on two scales--Mahler's baseline dyspnea index (BDI/TDI) and the Medical Research Council (MRC) scale. We sought to observe the factor or factors having the greatest impact on the quality of life of such patients. MATERIAL AND METHODS: Fifty-five patients diagnosed of COPD in stable phase of disease participated. Al underwent lung function testing at rest and during exercise (shuttle walking test with increasing loads and an exercise cycle test). Quality of life was assessed on the validated Spanish translation of the Chronic Respiratory Disease Questionnaire, which refers specifically to COPD. Baseline dyspnea was measured using Mahler's BDI/TDI and the MRC scale. RESULTS: Mean patient age was 63 +/- 9.5 years and FEV1 was 40 +/- 16.9%. Overall quality of life and each sub-item correlated significantly with mean dyspnea on both scales (BDI/TDI and MRC). Effort was weakly correlated and function parameters at rest were unrelated. Multiple correlation analysis showed that baseline dyspnea (BDI/TDI) was the most important predictor of quality of life. CONCLUSIONS: Dyspnea, particularly when expressed as BDI/TDI but also as measured on the MRC scale, correlates more highly with quality of life than does any other parameter. This indicates that dyspnea has greater impact than other factor on quality of life and that BDI/TDI provides a good baseline assessment of dyspnea in COPD patients.

[Blood levels of eosinophil cationic protein in patients with allergic rhinitis. Evolution after treatment with corticoids]. / Niveles séricos de proteína catiónica del eosinófilo en pacientes con rinitis alérgica. Evolución tras tratamiento con corticoides.

We analyze changes in eosinophilic cationic protein (ECP) serum levels after treatment with intranasal corticoids. Fifty-three healthy individuals (control group) and 21 patients diagnosed of allergic rhinitis, with or without bronchial asthma, were enrolled at a time when they had only nasal symptoms. Data were collected from skin Prick tests, forced spirometry, methacholine challenge, and complete blood workups, including IgE measurement, eosinophil counts and ECP serum levels determined by immunofluorescence. The patients received intranasal budesonide at a dose of 200 micrograms/24 h. ECP levels and eosinophil counts were determined before (baseline levels) and during treatment (on days 21 and 60). We found significant differences (p < 0.01) in baseline ECP levels of the controls (9.34 +/- 5.76) and patients (16.47 +/- 15.28). These values were significantly lower than baseline 21 and 60 days after treatment, although the changes between days 21 and 60 were not significant. Eosinophil counts did not fall significantly. We also found that eosinophil counts and ECP levels were correlated (r = 0.53) at baseline but not after treatment (r = 0.25). No patient experienced bronchial symptoms during the study. We conclude that ECP serum levels in patients with symptoms of rhinitis are significantly higher than levels in non symptomatic individuals. These levels fall significantly, possibly due to intranasal corticoid treatment, although eosinophil counts remain constant. ECP levels can therefore be used to monitor inflammatory activity in patients with allergic rhinitis.

[Inflammation mediators (eosinophilic cationic protein, ECP) in a normal population and in patients with bronchial asthma or allergic rhinitis]. / Mediadores de la inflamación (proteína catiónica del eosinófilo, ECP) en población normal y pacientes con asma bronquial o rinitis alérgica.

We analyzed serum levels of eosinophilic cationic protein (ECP), one of the 4 main eosinophilic proteins; ECP is released from an activated cell and acts as a mediator of inflammation. Serum samples from 139 persons were studied prospectively. Fifty-three individuals from the general population provided the control group. Eighty-six consecutive patients were also studied: 69 with bronchial asthma and 17 with allergic rhinitis and no signs of asthma. The level of severity of disease was established in the asthmatics by the method proposed by Aas (Aas score), based on symptoms and medications received within the last year. We also classified these patients as having mild, moderate or severe asthma according to the latest criteria issued by the International Consensus for Diagnosis and Treatment of Asthma. Atopic status was estimated by skin Prick tests. ECP levels in the control group (9.34 +/- 5.76 micrograms/l) were significantly lower (p < 0.001) than those of the total population of patients (17.59 +/- 16.85 micrograms/l). The mean for patients with rhinitis was 14.76 +/- 10.94 micrograms/l, whereas it was 18.29 +/- 18 micrograms/l in the asthmatics; the levels for both groups were statistically different from that of the control group (p < 0.03 and p < 0.001, respectively). Levels by degrees of severity established at the time of revision and by sensitivity to allergens were also significantly different from the level of the control group, although the mean levels were low in the group of severely affected patients who had received treatment with inhaled corticoids.(ABSTRACT TRUNCATED AT 250 WORDS)