[Outcome of two patients with Hurler's syndrome under enzyme replacement therapy with human recombinant alpha-L-iduronidase]. / Evolución de dos pacientes con síndrome de Hurler en tratamiento con enzima recombinante humana alpha-L-iduronidasa.

We performed a prospective study of two patients with Hurler's syndrome (aged 4.8 years and 17 months at the beginning of the intervention) under enzyme replacement therapy with human recombinant alpha-L-iduronidase for 452 and 28 weeks respectively. The aim of this study was to analyze the safety and efficacy of the intervention during the treatment periods. Several diagnostic imaging tests, clinical examinations, and serial laboratory determinations were performed to demonstrate the effectiveness of the therapy in both patients. In patient 1 (a boy aged 4.8 years, homozygote W402X), the treatment was always intended to be palliative because of the advanced stage of the disease. In patient 2 (a 17-month-old girl, heterozygote W402X) the treatment was initiated early with subsequent clinical stabilization without acquisition of regressive factors. Bone marrow transplantation from an unrelated donor was successful. Currently, because of the lack of histocompatible bone marrow donors, transplantation of hematopoietic stem cells from umbilical cord blood or peripheral blood are being performed with satisfactory results. In the future, gene therapy may be able to prevent the diseases associated with Hurler's syndrome and halt the neurocognitive deterioration characteristic of these patients.

Characteristics of continuous esophageal pH-metering in infants with gastroesophageal reflux and apparent life-threatening events.

Episodes of apnea during the first year of life have been classified with the term "Apparent Life-Threatening Events" (ALTE). Gastroesophageal reflux (GER) has been accepted to be one of the factors which can favor ALTE. The aim of this work is to study the continuous 24 h gastroesophageal pH-metering (fundamentally the Reflux Index [RI] and the Area Under Curve [AUC] parameters in three different periods of time: total pH-metering, pH-metering excluding the first two post-prandial hours, and pH-metering during sleep time, for 24 infants, 14 with ALTE and 10 without it). Between these two groups (with and without ALTE) there were no significant differences in the total pH-metering concerning the RI (2 +/- 1.2 vs 5.6 +/- 7.5 p > 0.05) and concerning the AUC (24.9 +/- 14.4 vs 67.4 +/- 84 p > 0.05), but in the analysis of the sleep period, the RI (p < 0.05) and the AUC (p < 0.01) both showed significant differences in the group of infants without ALTE. These results confirm that pH-metering study during sleep is the procedure of choice for recognizing infants with ALTE.

[Psychogenic cough: Another etiology for persistent cough]. / Tos psicógena: una causa de tos crónica.

The most common causes of persistent cough are upper respiratory tract disease (postnasal drip syndrome, infections) and asthma. In the last year, six patients (four boys and two girls), aged 7-12 years old, with a diagnosis of hard-to-manage asthma and/or persistent cough were referred to our department. All the patients had undergone treatment with multiple drugs for long periods without favorable clinical response. The findings of physical examination, radiology, basal pulmonary function and post-bronchodilation and fibrobronchoscopy were normal. Organic disease was ruled out and a psychiatric evaluation was performed. Intelligence quotient was in the lower normal range and generalized anxiety order was identified, thus establishing a diagnosis of psychogenic cough. Treatment consisted of relaxation techniques and psychopedagogic support with favorable outcome. To avoid diagnostic errors and inappropriate treatment, psychogenic cough should be included in the differential diagnosis of persistent cough and hard-to-manage asthma.

[Comparative efficacy of oral deflazacort versus oral prednisolone in children with moderate acute asthma]. / Estudio comparativo de la eficacia del deflazacort frente a prednisolona en el tratamiento de la crisis asmática moderada.

OBJECTIVES: To assess the efficacy and tolerability of oral deflazacort versus oral prednisolone in acute moderate asthma in children. PATIENTS AND METHODS: We performed a prospective, randomized, parallel group trial of children aged 6 to 14 years old with a diagnosis of asthma who presented to the pediatric emergency department for moderate asthma exacerbation. All patients were administered short-acting beta2-adrenergic agonists. The intervention groups received either oral deflazacort (1.5 mg/kg) or prednisolone (1 mg/kg) for 7 days. The primary outcome measure was forced expiratory volume in 1 second (FEV1) and secondary outcome measures were pulmonary symptom score index, peak expiratory flow rate (PEFR), hospitalization rate and the use of rescue beta2-agonists. Patients were evaluated at the start of treatment (visit 1), on day 2 (visit 2) and on day 7 (visit 3). RESULTS: Of the 54 children enrolled, two were hospitalized on visit 2 (one from each group). Baseline clinical data were similar in both groups: FEV1: 53 and 51 %; bronchodilator test: 119 and 121 %; PEFR: 169 and 165 L/min; symptom score: 6 and 6.5 for the deflazacort and prednisolone groups, respectively. On visit 2, all measures improved: FEV1: 122.2 and 126.5 % (p < 0.05); PEFR: 164 and 149 L/min (p < 0.05); symptom score: -4.4 and -3.8 (p < 0.05), without significant differences between groups. On visit 3 all variables continued to show improvement: FEV1: 133.2 and 132.5 % (p < 0.05); PEFR: 1115.7 and 187.6 L/min (p < 0.05); symptom score: -5.4 and -5.9 (p < 0.05), without significant differences between groups. No adverse effects were reported. CONCLUSIONS: Deflazacort and prednisolone show similar efficacy in improving pulmonary function and in producing clinical improvement in the management of acute moderate asthma in children.

[Bronchiolitis obliterans: outcome in the medium term]. / Bronquiolitis obliterante. Evolución a medio plazo.

BACKGROUND: Bronchiolitis obliterans is a chronic obstructive lung disease that follows a severe insult to the lower respiratory tract. Severity and outcome are different depending on the geographic area. The aim of this study was to communicate the results of our sample. METHODS: A retrospective study was performed in a sample of boys and girls with a medical diagnosis of bronchiolitis obliterans (BO) between December 1994 and February 2011. The diagnosis was made by high-resolution computed tomography (HRCT) scan and lung function. Lung biopsy was performed in one case. Pulmonary function testing included; forced spirometry (≥ 3 years old), plethysmography (≥ 5 years), bronchodilator tests (BDT), single-breath determination of carbon monoxide uptake in the lung (D(LCO)) (≥ 6 years) and measurement of exhaled lower respiratory nitric oxide (FE(NO)). Quantitative variables were; age at diagnosis, respiratory morbidity before the diagnosis, time from the start of the symptomatology until the diagnosis, follow-up time, respiratory morbidity after the diagnosis, airway specific resistance (sR(eff)), airway specific conductance (sG(eff)), residual volume, total lung capacity, thoracic gas volume, FEV(1), FVC, FEV(1)/FVC, FEF(25-75), D(LCO) and FE(NO). Qualitative variables were; sex, reason for consulting, viral infections, atopy, smoke exposure, HRCT scan and current treatment. Descriptive analysis was performed and pulmonary function before and after BDT was studied using paired-sample Wilcoxon and Student́s t-test. RESULTS: We studied a cohort of 22 cases, 10 (45.4%) boys and 12 (54.5%) girls. The mean age at the diagnosis was 4.87 ± 3, 27 years old. The follow-up period was 5 years (range 1 to 8 years). Related virus were; influenza 2 (9.09%), parainfluenza 2 (9.09%), adenovirus 3 (13.69%), syncytial respiratory virus 1 (4.5%) and rhinovirus 1 (4.54%). HRCT scan: mosaic pattern of lung attenuation 22 (100%) and bronchiectasis 8 (36.36%). Lung function at diagnosis showed fixed airflow obstruction and increased lung volumes. The global analysis showed a progressive decrease in FEV(1), FVC, FVC/FEV(1,) FEF(25-75) and increase in sR(eff) and residual volume with decrease in sG(eff). Individually, there was a tendency to stabilise the lung function comparing with initial values at diagnosis. Respiratory morbidity was low after the diagnosis. CONCLUSIONS: In most cases, fixed air-flow obstruction and lung function stability with low respiratory morbidity were observed. HRCT scan and lung function testing supported the diagnosis.

Association among lung function, exhaled nitric oxide, and the CAN questionnaire to assess asthma control in children.

BACKGROUND: The aim of this study was to investigate the association among a validated symptom-based questionnaire for asthma control in children (CAN), forced expiratory volume in 1 sec (FEV(1)), and fractional exhaled nitric oxide (FE(NO)). METHODS: Observational cross-sectional study was performed in a consecutive sample of asthmatic children aged between 7 and 14 years old from December 2007 to February 2008. FE(NO) was measured with a portable electrochemical analyzer and forced spirometry was performed according to American Thoracic Society/European Respiratory Society. The CAN questionnaire was completed by the parents (aged <9 years old) or by the children (> or = 9 years old). The strength of the association among FEV(1), FE(NO), and CAN questionnaire was studied using Spearman's rho, and the degree of agreement for asthma control among FEV(1), FE(NO), and CAN questionnaire, with classification of these variables according to values of normality, was studied using Pearson's chi(2) test and Cohen's kappa (KC). RESULTS: We studied 268 children, mean age 9.7 +/- 2.1 years. Significant correlations were found between FE(NO) and CAN (r = 0.2), between FEV(1) and CAN (r = -0.3), and between FE(NO) and FEV(1) (r = -0.12). On classifying the variables according to values of normality, no agreement was found to establish the degree of asthma control between FE(NO) and CAN (KC = 0.18, chi(2) Pearson = 9.63); between FEV(1) and CAN (KC = 0.29, chi(2) = 38.5); or between FE(NO) and FEV(1) (KC = 0.07, chi(2) = 4.9). CONCLUSIONS: The association among the three measurement instruments used to assess asthma control (FEV(1), FE(NO), and CAN) was weak. These are instruments that quantify variables that influence asthma in different ways, in this sense, none can be used instead of another in asthma management although they are complementary.

[The excretion of free cortisol in the urine in healthy children and in asthmatics treated with long-term inhaled glucocorticoids]. / Excreción de cortisol libre en orina en niños sanos y en asmáticos tratados con glucocorticoides inhalados a largo plazo.

OBJECTIVE: To assess urinary free cortisol (UFC) excretion in 24 hour urine samples collected from asthmatic children treated with inhaled glucocorticoids (IGC). PATIENTS AND METHODS: A retrospective cohort study was performed on a group of 358 children between the ages of 3 and 14 years. The children were divided into two groups, a normal population (n = 108) and an asthma group (n = 250). These children were treated uninterruptedly with IGC (mean dose 676 micrograms/day) during 17 +/- 8 months with budesonide (n = 221) or beclomethasone (n = 29) in dry powder (n = 167) or MDI with spacer chamber (n = 83). We considered the 24 hour urine sample valid when creatinine levels in blood and urine, as well as creatinine clearance, were normal. We determined UFC with a specific direct radioimmunoassay after cortisol extraction with dichloromethane. We performed a short ACTH test to assess the subnormal adrenocortical function when UC excretion in AG was less than -1SD. RESULTS: UFC excretion was 81.98 +/- 32.12 nmol/m2/day in the asthma group. There was no correlation between UFC and the mean dose of IGC, total dose given, device used for inhalation, time of treatment or oral glucocorticoid series. The subgroup treated with beclomethasone presented UF rates lower than the subgroup treated with budesonide. Except for two cases, the ACTH test performed in the AG had normal adrenocortical responses. CONCLUSION: 1) We established the normal values for UFC excretion in our pediatric population. 2) The long term asthma treatment with glucocorticoids at mean doses of 650 micrograms l/m2/day decrease physiologically the UFC excretion since the adrenocortical response remains within the normal range.

Bronquiolitis obliterante. Evolución a medio plazo / Bronchiolitis obliterans: Outcome in the medium term

Introducción: La bronquiolitis obliterante es una enfermedad respiratoria obstructiva crónica de la vía respiratoria inferior que se presenta principalmente después de infecciones víricas. La evolución a medio plazo difiere según el área geográfica. El objetivo ha sido comunicar los resultados en nuestro medio. Material y métodos: Estudio retrospectivo de casos diagnosticados de bronquiolitis obliterante (BO) entre diciembre-1994 y febrero-2011. El diagnóstico se estableció mediante TCAR pulmonar y función pulmonar; un caso precisó biopsia pulmonar. La exploración funcional se realizó con espirometría forzada (≥3 años de edad), pletismografía (≥5 años), pruebas de broncodilatación (PBD), difusión de monóxido de carbono (DLCO) (≥6 años) y óxido nítrico exhalado (FENO).Variables cuantitativas: edad al diagnóstico, morbilidad respiratoria antes del diagnóstico, tiempo de evolución hasta diagnóstico y de seguimiento, morbilidad respiratoria tras diagnóstico, resistencia (sReff) y conductancia específica de la vía aérea (sGeff), volumen residual, capacidad pulmonar total, volumen de gas intratorácico, FEV1, FVC, FEV1/FVC, FEF25-75, DLCO y FENO. Variables cualitativas: sexo, motivo de consulta, infecciones virales, atopia, tabaquismo, TCAR pulmonar y tratamiento. Análisis descriptivo y estudio de patrón de función pulmonar antes y después de PBD mediante t de Student y test de Wilcoxon para muestras apareadas. Resultados: Cohorte de 22 casos, 10 (45,4%) niños y 12 (54,5%) niñas. Edad media al diagnóstico 4,87±3,27 años. El tiempo de seguimiento fue 5 años (rango 1-8 años). Virus relacionados con BO: influenza 2 (9,09%), parainfluenza 2 (9,09%), adenovirus 3 (13,69%), virus respiratorio sincitial 1 (4,5%) y rinovirus 1 (4,54%). TCAR pulmonar: patrón en mosaico en 22 (100%) y bronquiectasias en 8 (36,36%). Función pulmonar al diagnóstico: patrón obstructivo fijo e incremento de volúmenes pulmonares. El análisis global evolutivo constató disminución progresiva de FEV1, FVC, FVC/FEV1 y FEF25-75 e incremento de sReff y volumen residual con disminución de sGeff. Individualmente, hay tendencia a la estabilidad de la función pulmonar respecto a valores al diagnóstico. Morbilidad respiratoria baja tras diagnóstico. Conclusiones: En la mayoría de los casos se objetiva patrón funcional obstructivo fijo y estabilidad evolutiva de la función pulmonar con morbilidad respiratoria baja. La TCAR pulmonar y la función pulmonar son las pruebas diagnósticas que apoyan el diagnóstico(AU)

Background: Bronchiolitis obliterans is a chronic obstructive lung disease that follows a severe insult to the lower respiratory tract. Severity and outcome are different depending on the geographic area. The aim of this study was to communicate the results of our sample. Methods: A retrospective study was performed in a sample of boys and girls with a medical diagnosis of bronchiolitis obliterans (BO) between December 1994 and February 2011. The diagnosis was made by high-resolution computed tomography (HRCT) scan and lung function. Lung biopsy was performed in one case. Pulmonary function testing included; forced spirometry (≥ 3 years old), plethysmography (≥ 5 years), bronchodilator tests (BDT), single-breath determination of carbon monoxide uptake in the lung (DLCO) (≥ 6 years) and measurement of exhaled lower respiratory nitric oxide (FENO). Quantitative variables were; age at diagnosis, respiratory morbidity before the diagnosis, time from the start of the symptomatology until the diagnosis, follow-up time, respiratory morbidity after the diagnosis, airway specific resistance (sReff), airway specific conductance (sGeff), residual volume, total lung capacity, thoracic gas volume, FEV1, FVC, FEV1/FVC, FEF25-75, DLCO and FENO. Qualitative variables were; sex, reason for consulting, viral infections, atopy, smoke exposure, HRCT scan and current treatment. Descriptive analysis was performed and pulmonary function before and after BDT was studied using paired-sample Wilcoxon and Student's t-test. Results: We studied a cohort of 22 cases, 10 (45.4%) boys and 12 (54.5%) girls. The mean age at the diagnosis was 4.87±3, 27 years old. The follow-up period was 5 years (range 1 to 8 years). Related virus were; influenza 2 (9.09%), parainfluenza 2 (9.09%), adenovirus 3 (13.69%), syncytial respiratory virus 1 (4.5%) and rhinovirus 1 (4.54%). HRCT scan: mosaic pattern of lung attenuation 22 (100%) and bronchiectasis 8 (36.36%). Lung function at diagnosis showed fixed airflow obstruction and increased lung volumes. The global analysis showed a progressive decrease in FEV1, FVC, FVC/FEV1, FEF25-75 and increase in sReff and residual volume with decrease in sGeff. Individually, there was a tendency to stabilise the lung function comparing with initial values at diagnosis. Respiratory morbidity was low after the diagnosis. Conclusions: In most cases, fixed air-flow obstruction and lung function stability with low respiratory morbidity were observed. HRCT scan and lung function testing supported the diagnosis(AU)

Evolución de dos pacientes con síndrome de Hurler en tratamiento con enzima recombinante humana α -L-iduronidasa / Outcome replacement of two patients with Hurler´s syndrome under enzyme replacement therapy with human recombinant α -L-iduronidase

Estudio prospectivo de 2 pacientes con enfermedad de Hurler (de 4,8 años y 17 meses de edad al inicio de la intervención) en tratamiento enzimático sustitutivo con enzima recombinante humana α -L-iduronidasa durante 52 y 28 semanas, respectivamente, con el objetivo de analizar la eficacia y seguridad de la intervención durante dicho período de tiempo. Se realizaron para ello diversas pruebas diagnósticas por imagen, exámenes clínicos y analíticos seriados que demostraron en ambos casos ser una terapia efectiva. En el caso 1 (varón de 4,8 años, homocigoto W402X) la intervención se planteó con fines paliativos desde el comienzo debido a su estado clínico muy evolucionado. En el caso 2 (mujer de 17 meses, heterocigota para W402X) la intervención se realizó de forma precoz y se observó una estabilización clínica posterior sin la adquisición de factores regresivos. Posteriormente se realizó con éxito un trasplante de médula ósea de donante no emparentado. Actualmente, ante la carencia de donantes de médula ósea histocompatibles, se está realizando trasplante de células madre hematopoyéticas procedentes de cordón o de sangre periférica con resultados satisfactorios. La terapia génica se considera el tratamiento futuro capaz de prevenir la enfermedad asociada al síndrome de Hurler y detener el deterioro neurocognitivo característico de estos pacientes.

We performed a prospective study of two patients with Hurler's syndrome (aged 4.8 years and 17 months at the beginning of the intervention) under enzyme replacement therapy with human recombinant α -L-iduronidase for 452 and 28 weeks respectively. The aim of this study was to analyze the safety and efficacy of the intervention during the treatment periods. Several diagnostic imaging tests, clinical examinations, and serial laboratory determinations were performed to demonstrate the effectiveness of the therapy in both patients. In patient 1 (a boy aged 4.8 years, homozygote W402X), the treatment was always intended to be palliative because of the advanced stage of the disease. In patient 2 (a 17-month-old girl, heterozygote W402X) the treatment was initiated early with subsequent clinical stabilization without acquisition of regressive factors. Bone marrow transplantation from an unrelated donor was successful. Currently, because of the lack of histocompatible bone marrow donors, transplantation of hematopoietic stem cells from umbilical cord blood or peripheral blood are being performed with satisfactory results. In the future, gene therapy may be able to prevent the diseases associated with Hurler's syndrome and halt the neurocognitive deterioration characteristic of these patients

Tos psicógena: una causa de tos crónica / Psychogenic cough: another etiology for persistent cough

Las enfermedades de la vía aérea superior (síndrome de goteo nasal posterior, infecciones) y el asma son las causas más habituales de la tos crónica. Durante el último año, nos fueron remitidos 6 casos (4 varones y 2 mujeres) de 7 a 12 años de edad, con el diagnóstico de asma de difícil control y/o tos persistente. Todos habían recibido tratamientos con múltiples fármacos durante largos períodos de tiempo, sin respuesta clínica favorable. La exploración física, radiología, función pulmonar basal y posbroncodilatación y fibrobroncoscopia, fueron normales. Descartada la enfermedad orgánica se realizó estudio psiquiátrico, constatando un coeficiente de inteligencia en el límite bajo de la normalidad y un trastorno por ansiedad generalizada, estableciéndose el diagnóstico de tos psicógena. El tratamiento se efectuó con técnicas de relajación y tratamiento psicopedagógico de apoyo, y evolucionaron favorablemente. La tos psicógena es un proceso que debe incluirse en el diagnóstico diferencial de tos crónica y en el asma de difícil control, con el fin de evitar errores diagnósticos y tratamientos inadecuados (AU)

Estudio comparativo de la eficacia del deflazacort frente a prednisolona en el tratamiento de la crisis asmática moderada / Comparative efficacy of oral deflazacort versus oral prednisolone in children with moderate acute asthma

Objetivos Evaluar la eficacia y tolerancia del deflazacort frente a la prednisolona en el tratamiento de la agudización moderada de asma en niños. Pacientes y métodos Estudio de intervención, multicéntrico, prospectivo, abierto, aleatorizado, grupos paralelos en niños de 6 a 14 años diagnosticados de asma, en situación de agudización moderada tratados todos con agonistas Beta2-adrenérgicos de corta acción. Los grupos de intervención recibieron deflazacort (1,5 mg/kg) o prednisolona (1 mg/kg) durante 7 días. La medida principal de eficacia fue el volumen espiratorio forzado en el primer segundo (FEV1) y como medidas secundarias se evaluaron la escala clínica de gravedad, el flujo espiratorio máximo (PEF), el índice de hospitalización y la utilización de medicación Beta2-agonista de rescate. Todos los sujetos fueron controlados al inicio del tratamiento (visita 1), al segundo día (visita 2) y al séptimo día (visita 3) del estudio. Resultados Se incluyeron en el estudio 54 pacientes, de los cuales dos requirieron hospitalización (uno de cada grupo). Los valores iniciales fueron similares para ambos grupos: FEV1, 53 y 51 por ciento; test de broncodilatación, 19 y + 21 por ciento;PEF, 169 y 165 l/min; escala de gravedad, 6,1 y 6,5 para los grupos deflazacort y prednisolona, respectivamente. En la visita 2, todos los parámetros mostraron mejoría: FEV1, +22,2 y 26,5 por ciento (p < 0,05); PEF, +64 y 49 l/min (p < 0,05); escala de gravedad -4,4 y -3,8 (p < 0,05), sin diferencias significativas entre ambos grupos. En la visita 3 todos los parámetros continuaron mejorando: FEV1, +33,2 y +32,5 por ciento (p < 0,05); PEF, +115,7 y 87,6 l/min (p < 0,05); escala de gravedad -5,4 y -5,9 (p < 0,05), también sin diferencias significativas entre los dos grupos. No se registraron efectos adversos en ningún paciente. Conclusiones En el tratamiento de la agudización moderada de asma en niños, deflazacort tiene una eficacia similar a prednisolona como se refleja tanto en la mejoría clínica de los pacientes como en la función pulmonar (AU)