Riesgo cardiometabólico en niños con obesidad grave / Cardiometabolic risk in children with severe obesity

Introducción: la obesidad grave ha tenido un mayor aumento que la obesidad no grave en los escolares chilenos durante los últimos años. Desconocemos si el punto de corte actualmente utilizado para definir la obesidad grave (IMC ≥ + 3 DE, curvas OMS-2007) se asocia a un mayor daño biológico en nuestra población pediátrica. Objetivo: describir y comparar el riesgo cardiometabólico en escolares con obesidad grave y no grave. Método: se realizó un análisis secundario de una muestra de 3325 escolares en los que se estudiaron los factores de riesgo cardiometabólico. Se comparó la prevalencia de estos factores en los que presentaban obesidad según fuera esta grave o no, calculándose los OR respectivos. Resultados: de los 589 sujetos con obesidad, con una media de edad de 11,4 ± 0,98 años, el 46 % eran de género femenino y el 11,5 % presentaban obesidad grave, con mayor prevalencia de la mayoría de los factores estudiados y sin diferencias en cuanto a antecedentes parentales de enfermedad crónica u obesidad, educación de los padres y actividad física del niño. Los niños con obesidad grave tenían un mayor riesgo de obesidad central (OR: 12,9), resistencia insulínica (OR: 3,2), HTA (OR: 2,67) y síndrome metabólico (OR:1,92). Conclusión: esta definición de obesidad grave en la niñez favorece la identificación de los niños con mayor comorbilidad cardiometabólica, lo cual permite focalizar los esfuerzos de prevención secundaria y su tratamiento más oportuno (AU)

Introduction: severe obesity has had a greater increase than non-severe obesity in Chilean schoolchildren during the last years. We do not know whether the cut-off point currently used to define severe obesity in children (BMI ≥ + 3 DE, WHO-2007 curves) is associated with a greater biological risk in our population. Objective: to describe and compare cardiometabolic risk in schoolchildren with severe vs. non-severe obesity. Methods: a secondary analysis of a sample of 3,325 schoolchildren was performed, in which cardiometabolic risk factors were studied. The prevalence of these was compared in the subsample of 589 schoolchildren with obesity according to whether it was severe or not, and the respective ORs were calculated. Results: mean age was 11.4 ± 0.98 years, 46 % were girls, and 11.5 % of the sample had severe obesity, with a higher prevalence of most of the factors studied and no differences in chronic disease, obesity or education in parents, or physical activity of the child. The risk of those with severe obesity for central obesity, insulin resistance, high blood pressure, and metabolic syndrome reached an OR of 12.9, 3.2, 2.67, and 1.92, respectively, as compared to those with non-severe obesity. Conclusion: this definition of severe obesity in childhood favors the identification of children with higher cardiometabolic comorbidity, which allows to focus the efforts of secondary prevention and its most timely treatment (AU)

Deficiencia de vitamina D y de hierro en niños y adolescentes con parálisis cerebral / Vitamin D and iron deficiencies in children and adolescents with cerebral palsy

INTRODUCCIÓN: Los niños y adolescentes con parálisis cerebral (PC) tienen mayor riesgo de desnutrición y deficiencias de micronutrientes. Dos de los que podemos estudiar y tratar son la vitamina D (VD) y el hierro. No disponemos de estudios que describan estas deficiencias en Chile. OBJETIVO: Describir el estado de ambos micronutrientes y evaluar la asociación con algunos factores que favorecen su déficit. Pacientes y método: Estudio descriptivo, corte transversal. Se estudiaron 69 sujetos, de entre 2 a 21años de edad, de dos hospitales públicos. Se obtuvieron datos demográficos, función motora, uso de sonda de alimentación y fármacos en uso. Se realizó evaluación nutricional según patrones para PC, y se determinó 25-hidroxivitaminaD (25OHD), ferritinemia y albuminemia. RESULTADOS: Edad promedio 11,1 ± 4,9 años, 43 (62,3%) varones, 56 (81,2%) tenían PC moderada-severa. Utilizaban sonda nasogástrica y/o gastrostomía 35 (50,7%), el 15,4% estaban con peso bajo y el 73,8% eutróficos, todos con talla normal. Recibían suplementación de VD 20 (29%), y de hierro, 4 (6,1%). La albuminemia fue normal en todos. El promedio de 25OHD fue 24,3 ± 8,8 ng/ml, 33 (47,8%) presentaron insuficiencia y 21 (30,4%) deficiencia. Tuvieron ferritina baja 36 (52,2%). No se encontró asociación entre 25OHD y variables estudiadas. Se encontró asociación entre ferritina baja y mayor edad (p = 0,03), ser hombre (p = 0,006) y uso de sonda de alimentación (p = 0,006). CONCLUSIONES: El grupo estudiado fue principalmente PC moderada-severa, con alta frecuencia de valores subóptimos de VD y baja ferritina plasmática, además de escasa suplementación de ambos. Sugerimos realizar seguimiento de 25OHD y ferritina, por su alta frecuencia de deficiencia y por contar con fármacos para su tratamiento en los hospitales públicos

INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitamin D (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. OBJECTIVE: To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21 years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitamin D (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean age was 11.1 ± 4.9 years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3 ± 8.8 ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P = .03), being male (P = .006), and feeding tube use (P = .006). CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies

Vitamin D and iron deficiencies in children and adolescents with cerebral palsy. / Deficiencia de vitamina D y de hierro en niños y adolescentes con parálisis cerebral.

INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. OBJECTIVE: To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies.

[An Early Obesity Prevention Program: HaViSa UC (2009-2019)]. / Un programa de prevención temprana de la obesidad: "HaViSa UC" (2009-2019).

INTRODUCTION: Prevention is the definitive solution to the serious nutritional epidemiological pro blem of children in our country and the world, obesity. OBJECTIVE: To describe the results of an obesi ty prevention program for infants and preschoolers, ten years after its implementation. SUBJECTS AND METHODS: Retrospective, and quasi-experimental study of the overweight and obesity prevalence, in children attending three nursery and preschool centers located at the Universidad Católica de Chile, since the implementation of a multidimensional program for early promotion of healthy lifestyle habits (HaViSa-UC) between 2009 and 2019. This study obtained ethical approval. Annual records of anthropometric assessment (WHO 2006) were analyzed using Minitab 17 software. The actions applied by the HaViSa-UC program were the assessment of nutritional status and communication with parents, delivery of healthy food, promotion of an active lifestyle, and education to encourage such healthy habits. RESULTS: The annual mean was 319 subjects, 14% younger than two years old, and 49.5% were girls. In March 2009 (baseline), 32.6% had overweight and 8.6% obesity; both figures decreased reaching 23.8% and 4.7% respectively, in March 2019. Normal weight increased from 56.9 to 67.4% and malnutrition presented no increase. In the same period, zW/H dropped from 0.84 ± 0.94 to 0.55 ± 0.87 (p: 0.00), and zH/A increased from -0.36 ± 0.87 to -0.32 ± 0.90 (p > 0.05). Con clusion: Since the implementation of the HaViSa-UC Program, the frequency of obesity decreased by 45.4% and overweight by 27.2% in this sample of infants and preschoolers, remaining stable after 10 years.

Un programa de prevención temprana de la obesidad: "HaViSa UC" (2009-2019) / An Early Obesity Prevention Program: HaViSa UC (2009-2019)

Resumen: Introducción: La prevención es la solución definitiva al grave problema epidemiológico nutricional de la niñez en nuestro país y el mundo, que es la obesidad. Objetivo: Describir los resultados de un programa de prevención de la obesidad en lactantes y preescolares, a diez años de su inicio. Sujetos y Método: Estudio retrospectivo, cuasi experimental, de la prevalencia de sobrepeso y obesidad, en niños y niñas asistentes a las salas-cuna y jardines infantiles de la Universidad Católica de Chile, desde la implementación en 2009 de un programa de promoción precoz de hábitos de vida saludable en alimentación y actividad física (HaViSa-UC), hasta 2019. Se obtuvo aprobación ética y se analizaron los registros anuales de las evaluaciones antropométricas (referencia OMS 2006), de cada mes de marzo, en los centros de tres campus universitarios, utilizando el programa Minitab 17. Las acciones implementadas por el HaViSa-UC fueron: evaluación del estado nutricional y comunicación con los padres, entrega de una alimentación saludable, promoción de un hábito activo de vida y educa ción para favorecer hábitos saludables de vida. Resultados: El promedio anual fue de 319 asistentes, 14% menores de dos años y 49,5% niñas. En marzo 2009 se detectó 32,6% de sobrepeso y 8,6% de obesidad, cifras que disminuyeron y se estabilizaron, alcanzando en marzo de 2019 a 23,8% y 4,7% respectivamente. Los eutróficos aumentaron desde 56,9% a 67,4%, sin aumentar el bajo peso. En el mismo período, zP/T bajó desde 0,84 ± 0,94 a 0,55 ± 0,87 (p = 0,00), y zT/E aumentó desde -0,36 ± 0,87 a -0,32 ± 0,90 (p > 0,05). Conclusión: Desde la implementación del programa HaViSa, en esta muestra de lactantes y preescolares la frecuencia de obesidad bajó en 45,4% y el sobrepeso en 27%, con estabilidad al cabo de diez años.

Abstract: Introduction: Prevention is the definitive solution to the serious nutritional epidemiological pro blem of children in our country and the world, obesity. Objective: To describe the results of an obesi ty prevention program for infants and preschoolers, ten years after its implementation. Subjects and Methods: Retrospective, and quasi-experimental study of the overweight and obesity prevalence, in children attending three nursery and preschool centers located at the Universidad Católica de Chile, since the implementation of a multidimensional program for early promotion of healthy lifestyle habits (HaViSa-UC) between 2009 and 2019. This study obtained ethical approval. Annual records of anthropometric assessment (WHO 2006) were analyzed using Minitab 17 software. The actions applied by the HaViSa-UC program were the assessment of nutritional status and communication with parents, delivery of healthy food, promotion of an active lifestyle, and education to encourage such healthy habits. Results: The annual mean was 319 subjects, 14% younger than two years old, and 49.5% were girls. In March 2009 (baseline), 32.6% had overweight and 8.6% obesity; both figures decreased reaching 23.8% and 4.7% respectively, in March 2019. Normal weight increased from 56.9 to 67.4% and malnutrition presented no increase. In the same period, zW/H dropped from 0.84 ± 0.94 to 0.55 ± 0.87 (p: 0.00), and zH/A increased from -0.36 ± 0.87 to -0.32 ± 0.90 (p > 0.05). Con clusion: Since the implementation of the HaViSa-UC Program, the frequency of obesity decreased by 45.4% and overweight by 27.2% in this sample of infants and preschoolers, remaining stable after 10 years.

[Morbimortality associated to nutritional status and feeding path in children with cerebral palsy]. / Morbimortalidad asociada al estado nutricional y vía de alimentación en niños con parálisis cerebral.

INTRODUCTION: Children and adolescents with cerebral palsy (CP) have a high prevalence of malnutrition associated to poor prognosis. For an adequate nutritional assessment, new growth curves (Brooks, 2011) are available, in which precise cut-off points in Weight/Age index correlate to increased morbidity and mortality rate. OBJECTIVE: To evaluate risk of hospitalization and death in patients with CP, according to nutritional risk (NR). PATIENTS AND METHOD: Observational and prospective cohort study of patients with CP in an outpatient referral center. We registered demographic, socioeconomic data and nutritional assessment. During a one-year follow-up, hospitalizations and mortality were recorded. The correspondent committee extended an ethical approval. RESULTS: 81 CP patients were recruit, age 131.6 ± 60.4 months (25-313), 60 % male, 77.5 % without independent mobility. The 23 NR patients (28.4%) had lower muscle and fat mass (p = 0.000). During the follow-up, 29/81 patients required hospitalization (35.8%) and 4/81 died (4.9%). There was not an increased risk of hospitalization and/or mortality in NR group, but both were significantly higher in gastrostomy-fed children (RR: 2,98 CI 95%: 1.32-6.75 combining both variables). CONCLUSIONS: In this study, children and adolescents with severe CP and nutritional risk had similar morbidity and mortality during a one-year follow-up, compared to those with acceptable nutritional status. Both risks were higher in gastrostomy-fed than the orally fed children.

[Recommendations from parents of obese children in treatment to the health-care team: qualitative study]. / Recomendaciones de padres de niños obesos en tratamiento para el equipo de salud: estudio cualitativo.

INTRODUCTION: The family plays an essential role in the adherence and effectiveness in the treatment of childhood obesity. Caregivers’ experience is fundamental for proper guidance. AIM: To describe the recommendations for the health-care team made by parents of children that are being treated for obesity. PATIENTS AND METHOD: Cross-sectional and descriptive study with a qualitative approach and purposeful sampling. In the first semester of 2015, interviews were conducted with nine parents of children from 4 to 10 years old that were being treated for obesity ad who had at least three medical appointments in the previous year. The data analysis was based on the Grounded Theory Approach through open coding. The study was ethically approved and informed parental consent was obtained. RESULTS: The results were grouped in the following main categories: a) Health-care team-caregiver relationship, b) Health-care team-child relationship, c) Encouraging family participation, d) Encouraging therapeutic adherence in the child and e) Frequency of medical appointments. CONCLUSION: From the perspective of this group of parents of obese children, the health-care team should establish a close therapeutic bond with the children and their parents during the treatment process, in addition to encouraging family participation. The importance of developing therapeutic interventions that consider the perspective of the patient’s system is emphasized.

Morbimortalidad asociada al estado nutricional y vía de alimentación en niños con parálisis cerebral / Morbimortality associated to nutritional status and feeding path in children with cerebral palsy

Introducción: Los niños y adolescentes con Parálisis Cerebral (PC) tienen elevada prevalencia de desnutrición, asociada a peor pronóstico. Para la adecuada evaluación nutricional existen nuevas curvas de crecimiento (Brooks y Col) que han planteado puntos de corte del índice Peso/Edad asociados a mayor morbimortalidad. Objetivo: Evaluar si pacientes con PC, en dicha categoría de riesgo nutricional (RN), presentan mayor riesgo de hospitalización y muerte. Pacientes y Método: Estudio observacional y prospectivo de una cohorte de pacientes con PC, controlados en un centro ambulatorio de referencia. Se registró: datos demográficos, socioeconómicos, evaluación funcional motora y nutricional basal. En seguimiento durante un año se constataron hospitalizaciones y mortalidad. Investigación aprobada por la comisión de ética. Resultados: Se reclutaron 81 niños con PC, edad 131,6 ± 60,4 meses (25-313), 60% de sexo masculino, 77,5% no se movilizaba por sí mismo. Los 23 pacientes con RN (28,4%), presentaban menor masa muscular y masa grasa (p = 0,000). Durante el año de seguimiento, 29 pacientes requirieron hospitalización (35,8%) y 4 fallecieron (4,9%). El grupo con RN no tuvo mayor morbilidad ni mortalidad que los sin RN. Sin embargo, ambos riesgos fueron mayores en los pacientes gastrostomizados versus los alimentados por vía oral (RR: 2,98 IC 95%: 1.32-6.75 al combinar ambas variables). Conclusiones: En esta cohorte de niños y adolescentes con PC seguidos durante un año, aquellos definidos como de riesgo nutricional según nuevas curvas, tuvieron similar morbimortalidad a los que tenían estado nutricional aceptable. La morbimortalidad fue mayor en los gastrostomizados.

Introduction: Children and adolescents with cerebral palsy (CP) have a high prevalence of malnutrition associated to poor prognosis. For an adequate nutritional assessment, new growth curves (Brooks, 2011) are available, in which precise cut-off points in Weight/Age index correlate to increased morbidity and mortality rate. Objective: To evaluate risk of hospitalization and death in patients with CP, according to nutritional risk (NR). Patients and Method: Observational and prospective cohort study of patients with CP in an outpatient referral center. We registered demographic, socioeconomic data and nutritional assessment. During a one-year follow-up, hospitalizations and mortality were recorded. The correspondent committee extended an ethical approval. Results: 81 CP patients were recruit, age 131.6 ± 60.4 months (25-313), 60 % male, 77.5 % without independent mobility. The 23 NR patients (28.4%) had lower muscle and fat mass (p = 0.000). During the follow-up, 29/81 patients required hospitalization (35.8%) and 4/81 died (4.9%). There was not an increased risk of hospitalization and/or mortality in NR group, but both were significantly higher in gastrostomy-fed children (RR: 2,98 CI 95%: 1.32-6.75 combining both variables). Conclusions: In this study, children and adolescents with severe CP and nutritional risk had similar morbidity and mortality during a one-year follow-up, compared to those with acceptable nutritional status. Both risks were higher in gastrostomy-fed than the orally fed children.

Recomendaciones de padres de niños obesos en tratamiento para el equipo de salud: estudio cualitativo / Recommendations from parents of obese children in treatment to the health-care team: qualitative study

Introducción: La familia tiene un rol fundamental en la adherencia y efectividad del tratamiento de la obesidad infantil; conocer la experiencia de los cuidadores es una herramienta valiosa a considerar. Objetivo: Describir las recomendaciones para el equipo de salud que efectúan los padres cuidadores de niños(as) en tratamiento por obesidad. Pacientes y Método: Estudio transversal, descriptivo, con enfoque cualitativo y muestreo intencionado. En el primer semestre del año 2015 se entrevistó a nueve padres de niños de 4 a 10 años de edad, en tratamiento por su obesidad y con al menos tres controles durante el año previo. El análisis de datos se basó en los planteamientos de la Grounded Theory, mediante codificación abierta. El estudio tuvo aprobación ética y se utilizó consentimiento informado. Resultados: Los datos fueron agrupados en cinco categorías principales: a) Relación equipo de salud-cuidador, b) Relación equipo de salud-niño(a), c) Promover la participación familiar, d) Motivar adherencia terapéutica en el niño(a) y e) Frecuencia de controles. Conclusiones: Desde la perspectiva de este grupo de padres de niños con obesidad, el rol del equipo de salud debe basarse en establecer un vínculo terapéutico cercano con los niños(as) y sus padres durante el proceso de tratamiento, además de promover la participación del grupo familiar. Se destaca la importancia de desarrollar intervenciones terapéuticas que consideren la perspectiva del sistema consultante.

Introduction: The family plays an essential role in the adherence and effectiveness in the treatment of childhood obesity. Caregivers’ experience is fundamental for proper guidance. Aim: To describe the recommendations for the health-care team made by parents of children that are being treated for obesity. Patients and Method: Cross-sectional and descriptive study with a qualitative approach and purposeful sampling. In the first semester of 2015, interviews were conducted with nine parents of children from 4 to 10 years old that were being treated for obesity ad who had at least three medical appointments in the previous year. The data analysis was based on the Grounded Theory Approach through open coding. The study was ethically approved and informed parental consent was obtained. Results: The results were grouped in the following main categories: a) Health-care team-caregiver relationship, b) Health-care team-child relationship, c) Encouraging family participation, d) Encouraging therapeutic adherence in the child and e) Frequency of medical appointments. Conclusion: From the perspective of this group of parents of obese children, the health-care team should establish a close therapeutic bond with the children and their parents during the treatment process, in addition to encouraging family participation. The importance of developing therapeutic interventions that consider the perspective of the patient’s system is emphasized.

Prenatal growth and metabolic syndrome components among Chilean children.

The association of prenatal growth with metabolic syndrome (MS) components and insulin resistance (IR) in children has not been studied in Chile and most developing countries. Some associations found in developed countries are controversial. A retrospective cohort study was designed linking present information on MS components and IR in children with register-based information on birth weight (BW), birth length (BL) and gestational age (GA). Examinations included anthropometry and blood pressure (BP), as well as self-report of pubertal status. A fasting blood sample was taken to determine lipids, glucose, insulin and homeostasis model assessment (HOMA)-IR was calculated. The study cohort of 2152 children was on average 11.4 ± 1.0 years old. The prevalence of MS, IR and overweight were 7.6%, 24.5% and 34%, respectively. Elevated BP was negatively associated with dichotomized risk categories of the perinatal factors studied (BW, BL and GA). Contingency tables showed that high waist circumference (WC) and elevated BP had a U-shaped association with various categories of BW and BL, respectively. Stepwise linear regressions selected: (a) WC as inversely associated to GA and directly associated to BW, (b) BP as inversely associated to GA and (c) HOMA-IR as inversely associated to BL. Non-optimal prenatal growth seems to predispose to high WC, elevated BP and IR in school-age children, supporting the early life origin of several non-communicable diseases. Those associations were rather weak as estimated by the slopes of the regressions and probably reduced by their U-shaped nature; they would reasonably become stronger with a longer follow-up.

Role of dispersion forces in the structure of graphene monolayers on Ru surfaces.

Elaborate density functional theory (DFT) calculations that include the effect of van der Waals (vdW) interactions have been carried out for graphene epitaxially grown on Ru(0001). The calculations predict a reduction of structural corrugation in the observed moiré pattern of about 25% (∼0.4 Å) with respect to DFT calculations without vdW corrections. The simulated STM topographies are close to the experimental ones in a wide range of bias voltage around the Fermi level.

Potential energy landscape for hot electrons in periodically nanostructured graphene.

We explore the spatial variations of the unoccupied electronic states of graphene epitaxially grown on Ru(0001) and observed three unexpected features: the first graphene image state is split in energy; unlike all other image states, the split state does not follow the local work function modulation, and a new interfacial state at +3 eV appears on some areas of the surface. First-principles calculations explain the observations and permit us to conclude that the system behaves as a self-organized periodic array of quantum dots.

Acute effect of ketotifen on the dose-response curve of histamine and methacholine in asthma.

This study was designed to assess the acute effect of 1 mg of orally administered ketotifen on the dose-response curve to both histamine and methacholine, in 15 patients with bronchial asthma. From this curve we measured the concentration that produced a 20% fall in FEV1 (PC20) and reactivity, defined as the slope of the curve beyond the threshold dose. Results were analysed comparing the change in log PC20 and in reactivity before and after a double-blind administration of ketotifen and placebo. Ketotifen, compared to placebo, significantly increased the histamine PC20 (P less than 0.001) and reduced reactivity (P less than 0.001). After adjusting for starting FEV1 the difference of effect between ketotifen and placebo was still significant, although to a lesser degree (P less than 0.01). In contrast, ketotifen did not modify the methacholine dose-response curve. No significant changes were observed in FEV1 after ketotifen. The results suggest that acute administration of ketotifen has a selective action on histamine-activated pathways of bronchoconstriction.