Cutoff point for exhaled nitric oxide corresponding to 3% sputum eosinophils.

BACKGROUND: The eosinophilic asthma phenotype (sputum eosinophils 3%) indicates a good response to corticosteroids and T(H)2 immunomodulators. Exhaled nitric oxide (FeNO) is rapidly measured by portable devices, and although it is not a selective marker of eosinophilic inflammation, several studies have demonstrated a strong correlation with it. We investigated which FeNO value was the best fit with 3% sputum eosinophils in asthma patients. METHODS: We included 129 consecutive, nonsmoking asthmatics who underwent skin tests, FeNO quantification (NIOX MINO), spirometry, and induced sputum analysis and completed the Asthma Control Test questionnaire. Receiver operating characteristic curves were constructed, and logistic regression analysis was performed. RESULTS: Symptoms were detected more frequently in the eosinophilic asthma group, as were higher airway obstruction and sensitivity to hypertonic saline. The FeNO cutoff point of 21 ppb was the best fit with 3% sputum eosinophilia. This value behaved better among corticosteroid-naïve patients (sensitivity, 97%; specificity, 58%; positive predictive value, 86%; negative predictive value, 88%) than among those receiving corticosteroids (sensitivity, 81%; specificity, 25%; positive predictive value, 74%; negative predictive value, 33%). CONCLUSION: FeNO ≥ 21 ppb is associated with airway eosinophilia. In corticosteroid-naïve patients, FeNO < 21 ppb enables us to rule out airway eosinophilia.

Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment.

Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli.

Cutoff point for exhaled nitric oxide corresponding to 3% sputum eosinophils

Background: The eosinophilic asthma phenotype (sputum eosinophils ≥3%) indicates a good response to corticosteroids and TH2 immunomodulators. Exhaled nitric oxide (FeNO) is rapidly measured by portable devices, and although it is not a selective marker of eosinophilic inflammation, several studies have demonstrated a strong correlation with it. We investigated which FeNO value was the best fit with 3% sputum eosinophils in asthma patients. Methods: We included 129 consecutive, nonsmoking asthmatics who underwent skin tests, FeNO quantification (NIOX MINO), spirometry, and induced sputum analysis and completed the Asthma Control Test questionnaire. Receiver operating characteristic curves were constructed, and logistic regression analysis was performed. Results: Symptoms were detected more frequently in the eosinophilic asthma group, as were higher airway obstruction and sensitivity to hypertonic saline. The FeNO cutoff point of 21 ppb was the best fit with 3% sputum eosinophilia. This value behaved better among corticosteroid-naïve patients (sensitivity, 97%; specificity, 58%; positive predictive value, 86%; negative predictive value, 88%) than among those receiving corticosteroids (sensitivity, 81%; specificity, 25%; positive predictive value, 74%; negative predictive value, 33%). Conclusion: FeNO ≥21 ppb is associated with airway eosinophilia. In corticosteroid-naïve patients, FeNO (AU)

Antecedentes: El fenotipo de asma eosinofílica (eosinófilos en esputo ≥3%) es un marcador de buena respuesta a corticosteroides y fármacos Th2 inmunomoduladores. La Fracción Exhalada de Óxido Nítrico (FENO) se puede medir de forma rápida y sencilla con dispositivos portátiles, y si bien no es un marcador selectivo de inflamación eosinofílica, numerosos estudios han mostrado que guarda una buena relación con ella. En el presente estudio, hemos evaluado qué valor de FENO discrimina mejor la eosinofilia en esputo ≥3%. Métodos: Incluimos 129 asmáticos no fumadores consecutivos a quienes se realizaron pruebas cutáneas, medición de FENO (Niox Mino), espirometría forzada e inducción de esputo. Los pacientes autocompletaron el Test de Control de Asma (ACT). Se realizaron curvas ROC y estudio estadístico de regresión logística. Resultados: El grupo con asma eosinofílica tenía más síntomas, mayor obstrucción basal y mayor sensibilidad bronquial al salino hipertónico. El valor de FENO de 21 ppb fue el punto de corte que mejor se ajustaba a la eosinofilia en esputo del 3%. Este indicador se comportaba mejor entre los pacientes sin tratamiento esteroideo (sensibilidad 97%, especificidad 58%, VPP 86%, VPN 88%) que entre los que recibían corticosteroides (sensibilidad 81%, especificidad 25%, VPP 74%, VPN 33%). Conclusión: Los valores de FENO ≥21 ppb se asocian a eosinofilia en esputo. En sujetos que no reciben tratamiento esteroideo, valores de FENO (AU)

[Eosinophils in induced sputum versus nitric oxide in exhaled air: clinical utility in bronchial asthma]. / Eosinofilia en esputo versus óxido nítrico en aire exhalado: aplicación clínica en el asma.

BACKGROUND: Assessment of eosinophils in induced sputum can help to optimize anti-inflammatory therapy in bronchial asthma, but this is a very demanding technique. The aim of the study is to compare nitric oxide in exhaled air (FeNO), an easy to measure inflammatory biomarker, with eosinophils in sputum in terms of relationship with clinical and functional parameters. METHODS: 106 asthmatic patients (50 in anti-inflammatory therapy [AB+] and 56 without it [AB-]) and 15 controls were included. After filling a clinical questionnaire, FeNO measurement, forced spirometry and sputum induction by bronchial challenge with hypertonic saline solution were performed. RESULTS: Adequate measurements of FeNO and eosinophils were obtained in 100% and 81% of the patients, respectively. FENO w were higher for AB- compared to AB+ and controls. The percentage of eosinophils in sputum was higher in asthmatic patients compared to controls but without differences between both asthmatics groups and was well correlated with the slope of the dose-response curve of bronchial challenge. In the AB- group, FeNO and eosinophils were well correlated with asthma control level. CONCLUSION: FENO measurement is readily available and well correlated with clinical and functional markers asthma expression. Anti-inflammatory therapy blunts FeNO levels compromising its utility in the long-term follow-up of asthma patients.

Eosinofilia en esputo versus óxido nítrico en aire exhalado: aplicación clínica en el asma / Eosinophils in induced sputum versus nitric oxide in exhaled air: clinical utility in bronchial asthma

Fundamento. La eosinofilia en esputo inducido permiteoptimizar el tratamiento antiinflamatorio en el asma perosus requerimientos técnicos hacen poco viable su aplicaciónclínica. Evaluamos si el óxido nítrico (FENO), un marcadorinflamatorio de fácil medición, podía suplir a la eosinofiliaen esputo, así como la relación que ambos índicesmostraban con aspectos clínicos y funcionales del asma.Métodos. Se estudiaron 106 asmáticos (50 con tratamientoantiinflamatorio [AB+] y 56 sin él [AB-]) y 15controles. Tras completar un cuestionario clínico, seles realizó medición de FENO, espirometría forzada e inducciónde esputo. Se calculó el valor de pendiente dela curva concentración-respuesta (CCR) obtenida trasla inhalación de salino hipertónico.Resultados. Los resultados de FENO y de eosinofilia enesputo fueron valorables en 100% y 81% de los casosrespectivamente. Los valores de FENO fueron superioresen AB- que en AB+ y en éstos respecto a controles. Laeosinofilia, mayor en asmáticos que en controles aunquesin diferencias entre AB+ y AB-, se correlacionó conla FENO y se comportó de forma paralela a la pendienteCCR. Había correlación entre el nivel de control delasma y los índices inflamatorios (eosinofilia y FENO) enel grupo AB- pero no en el AB+.Conclusión. La obtención de FENO es rápida, sencilla yda resultados inmediatos que se correlacionan con laactividad del asma. Puede desempeñar un papel relevanteen el diagnóstico y manejo terapéutico inicial deasma, aunque se necesitan más estudios para evaluarsu aplicación en la monitorización a largo plazo de laenfermedad, por la influencia tan notable que tiene sobresus niveles el tratamiento antiinflamatorio(AU)

Background. Assessment of eosinophils in inducedsputum can help to optimize anti-inflammatory therapyin bronchial asthma, but this is a very demanding technique.The aim of the study is to compare nitric oxidein exhaled air (FeNO), an easy to measure inflammatorybiomarker, with eosinophils in sputum in terms of relationshipwith clinical and functional parameters.Methods. 106 asthmatic patients (50 in anti-inflammatorytherapy [AB+] and 56 without it [AB-]) and 15 controlswere included. After filling a clinical questionnaire,FeNO measurement, forced spirometry and sputum inductionby bronchial challenge with hypertonic salinesolution were performed.Results. Adequate measurements of FeNO and eosinophilswere obtained in 100% and 81% of the patients,respectively. FENO w were higher for AB- compared toAB+ and controls. The percentage of eosinophils in sputumwas higher in asthmatic patients compared to controlsbut without differences between both asthmaticsgroups and was well correlated with the slope of thedose-response curve of bronchial challenge. In the ABgroup,FeNO and eosinophils were well correlated withasthma control level.Conclusion. FENO measurement is readily available andwell correlated with clinical and functional markersasthma expression. Anti-inflammatory therapy bluntsFeNO levels compromising its utility in the long-termfollow-up of asthma patients(AU)

[Analysis and detection of fibres in the pulmonary tissue]. / Análisis y detección de fibras en tejido pulmonar.

Microscopic techniques for the analysis of fibres in pulmonary tissue and bronchovesicular washing have provided information of great interest for a better understanding of diseases related to the inhalation of asbestos. These tests serve to help in establishing an individual estimation of previous exposure to asbestos. A mineralogical analysis of the concentration of intra-pulmonary fibres can be needed on some special occasions, for example when the data obtained from the occupational history are of scarce relevance or inconclusive. For these reasons, this type of study is increasingly used in clinical work and in resolving medico-legal problems, but the complexity of some of them makes the creation of reference laboratories useful as they make methodological homogenisation possible and facilitate the comparison of results. Plueropulmonary diseases related to inhaling asbestos are considered to be of occupational type and are therefore subject to a series of legal requisites for their recognition and possible compensation. A history of exposure with a suitable latency period, together with a compatible clinical-radiological picture, can be sufficient for the diagnosis but, in certain situations, such as when the exposure data are not precise, the analysis and detection of asbestos fibres in respiratory samples or from the pulmonary tissue can be clarifying.

Análisis y detección de fibras en tejido pulmonar / Analysis and detection of fibres in the pulmonary tissue

Las técnicas microscópicas para el análisis defibras en tejido pulmonar y lavado broncoalveolar hanaportado información de gran interés para un mejorentendimiento de las enfermedades relacionadas conla inhalación de asbesto. Estas pruebas sirven deayuda para establecer una estimación individual de laexposición previa al amianto.Un análisis mineralógico de la concentración defibras intrapulmonares puede ser necesario en algunasocasiones especiales, como por ejemplo cuando losdatos obtenidos en la historia ocupacional sean pocorelevantes o inconclusos.Por todo ello, este tipo de estudios se utiliza cadavez más en trabajos clínicos y en la resolución de problemasmedicolegales, pero la complejidad de algunode ellos hace conveniente la creación de laboratoriosde referencia que permitan la homogeneización metodológicay faciliten la comparación de resultados.Las enfermedades pleuropulmonares relacionadascon la inhalación al asbesto son consideradas como detipo profesional y, por tanto, están sujetas a una seriede requisitos legales para su reconocimiento y posiblecompensación. Una historia de exposición con períodode latencia adecuado, junto con un cuadro clínicoradiológicocompatible, puede ser suficiente para eldiagnóstico pero, en determinadas situaciones, comopor ejemplo cuando los datos de exposición no sonprecisos, el análisis y detección de fibras de asbesto enmuestras respiratorias o de tejido pulmonar puede seraclaratorio

Microscopic techniques for the analysis of fibresin pulmonary tissue and bronchovesicular washinghave provided information of great interest for abetter understanding of diseases related to theinhalation of asbestos. These tests serve to help inestablishing an individual estimation of previousexposure to asbestos.A mineralogical analysis of the concentration ofintra-pulmonary fibres can be needed on some specialoccasions, for example when the data obtained fromthe occupational history are of scarce relevance orinconclusive.For these reasons, this type of study isincreasingly used in clinical work and in resolvingmedico-legal problems, but the complexity of some ofthem makes the creation of reference laboratoriesuseful as they make methodological homogenisationpossible and facilitate the comparison of results.Plueropulmonary diseases related to inhalingasbestos are considered to be of occupational type andare therefore subject to a series of legal requisites fortheir recognition and possible compensation. A historyof exposure with a suitable latency period, togetherwith a compatible clinical-radiological picture, can besufficient for the diagnosis but, in certain situations,such as when the exposure data are not precise, theanalysis and detection of asbestos fibres in respiratorysamples or from the pulmonary tissue can beclarifying

Aplicación de las oncoproteínas p21RAS, p53, Bcl-2 y del factor de proliferación celular Ki-67(MIB-1) en el diagnóstico y pronóstico de tumores tiroideos / Value of the Expression of p21RAS, P53, Bcl-2 Oncoproteins and Ki-67(MIB-1) Antigen of Cellular Proliferation in the Diagnosis and Prognosis of Thyroid Tumours

Introducción. El tiroides es un buen órgano para estudiar las alteraciones genéticas en el desarrollo y progresión tumoral, siendo de interés estudiar marcadores de proliferación celular y oncogenes. Material y métodos. Se han estudiado 36 adenomas, 58 carcinomas papilares, 32 carcinomas foliculares , 2 carcinomas anaplásicos y 12 carcinomas medulares . Se han estudiado factores clínicos e histológicos relacionados con el pronóstico y mediante inmunohistoquímica se ha estudiado Ki-67(MIB-1), p53, Bcl-2 y p21 RAS. Resultados. Se obtienen diferencias estadísticas en el índice proliferativo Ki-67 (MIB-1) entre adenomas y carcinomas foliculares. La proteína p53 no se expresa en adenomas y lo hace en aquellos carcinomas con mayor desdiferenciación histológica. También se correlaciona con la edad avanzada, el mayor tamaño y progresión tumoral. La expresión de Bcl-2 es alta en tejido tiroideo normal y en adenomas, se conserva en carcinomas y disminuye en relación a la desdiferenciación histológica, perdiéndose totalmente en los carcinomas anaplásicos. En carcinomas medulares su pérdida se correlaciona con la mortalidad. La expresión intensa de la proteína p21 RAS se asocia significativamente en carcinomas papilares con estadios clínicos avanzados. Conclusiones. Las diferencias en la actividad proliferativa entre adenomas y carcinomas foliculares puede ayudar al diagnóstico diferencial. La expresión de p53 y la pérdida de expresión de Bcl-2 se correlacionan con el proceso de desdiferenciación histológica. La sobreexpresión de p21 RAS en carcinomas papilares se relaciona con la progresión tumoral (AU)

[Value of the expression of p21RAS, P53, Bcl-2 oncoproteins and Ki-67(MIB-1) antigen of cellular proliferation in the diagnosis and prognosis of thyroi]. / Aplicación de las oncoproteínas p21RAS, p53, Bcl-2 y del factor de proliferación celular Ki-67(MIB-1) en el diagnóstico y pronóstico de tumores tiroid.

INTRODUCTION: The thyroid gland is a good organ for the study of genetic alterations in tumoural development and progress. The study of oncogenes and antigens of cellular proliferation is of interest. MATERIAL AND METHODS: 36 cases of thyroid adenomas, 58 papillary carcinomas, 32 follicular carcinomas, 2 anaplastic carcinomas and 12 medullary carcinomas were selected. Clinical and histological prognostic factors were studied and an immunohistochemical study with Ki-67 (MIB-1), p53, Bcl-2 and p21 RAS antibodies was performed. RESULTS: The proliferative rate Ki-67 (MIB-1) showed statistical differences in adenomas and follicular carcinomas. The p53 protein did not appear in adenomas, but was shown in those carcinomas with bigger histological dedifferentiation. A relationship was also established with greater age, larger size and progression of the tumour. The Bcl-2 protein was high in the normal thyroid, in the adenomas and in the carcinomas, decreasing in correlation with histological dedifferentiation, and totally disappearing in the anaplastic carcinomas. In medullary carcinomas its disappearance was correlated with mortality. The intense expression of the p21 RAS protein in papillary carcinomas is statistically correlated with advanced clinical studies. CONCLUSIONS: The differences in the proliferative rate between adenomas and follicular carcinomas can be of help in differential diagnosis. The p53 manifestation and the loss of the Bcl-2 expression are correlated with the histological redifferentiation process. An intense manifestation of p21 RAS in papillary carcinoma is correlated with tumoural progression.

[Dysphagia as an unusual form of presentation of malignant pleural mesothelioma]. / Disfagia como forma de presentación inusual en mesotelioma pleural maligno.

Dysphagia is an unusual presenting symptom as of extradigestive tumors. Malignant mesothelioma, is a rare tumor localized in the pleural cavity in 80% of all cases and it rarely appears with dysphagia as first symptom. We describe the case of a 74-year-old woman admitted with progressive dysphagia for solid and liquid food, atypical epigastric pain, with in conclusive endoscopic and radiologic studies. Nuclear Magnetic Resonance established the diagnostic suspicion of malignant mesothelioma which was confirmed by the histologic study of a biopsy taken by thoracotomy. We think of interest to report this case of paraesophageal mesothelioma because of its unusual localization and presentation.

[Muscular tumors of the digestive tract: an analysis of 53 cases]. / Tumores musculares del tubo digestivo: análisis de 53 casos.

We present 53 cases of gastrointestinal smooth tumors (43 leiomyomas and 10 leiomyosarcomas) which have being diagnosed in Virgen del Camino Hospital during a period of 17 years. The aim of the research is to know the incidence of such tumors, their clinical presentation, the usefulness of radiologic and endoscopic studies for their diagnosis, as soon as to make a bibliographic revision of new diagnostic and therapeutic methods. This kind of tumor had an incidence of 3.1 cases per year. The symptomatology because of which the patients consulted depended on the location and the size of the tumors, though 18% of the cases were asymptomatic and were found in surgical operations. Endoscopic biopsy had a diagnostic sensibility of 28%; it didn't obstruct later exeresis. It has to be emphasized that, according to our bibliographic revision, there is a growing importance of endoscopic echography, not only as for diagnosis, but also as for non surgical treatment of this kind of tumor. Endoscopic resection can be a valid alternative for exeresis of small tumors (less than 2 cm according to some authors); haemorrhage is the most frequent complication, though it can be easily controlled.