Consultas a urgencia y valores espirométricos tras el reemplazo de salmeterol/fluticasona por budesonida/formoterol en pacientes con asma moderada a grave / Emergency consultations and spirometric values after replacement of salmeterol/fluticasone with budesonide/formoterol in patients with moderate to severe asthma

El asma se caracteriza por su impacto deletéreo que incluye gran coste económico para el sistema de salud. En pacientes con asma mal controlada a pesar del tratamiento, se propone un régimen de mantenimiento con corticoides inhalados y formoterol. El objetivo del presente estudio observacional retrospectivo fue evaluar las modificaciones espirométricas tras el cambio del medicamento controlador en pacientes con asma moderada a severa asistidos en el Hospital Clínico de Magallanes de Punta Arenas, así como también cuantificar la modificación en el número de exacerbaciones graves (consulta a un servicio de urgencia y/u hospitalización por asma). Participaron 61 adultos con asma moderada a severa (mediana de edad: 60 años [rango: 21-87], mujeres: 69,4%; comorbilidad atópica/alérgica: 79%; otras comorbilidades: 46,8%) en los que se cambió el tratamiento con fluticasona/salmeterol 250/25 μg por budesónida/formoterol 160/4,5 μg. No se observaron cambios significativos en los índices espirométricos tras el cambio. Con el tratamiento inicial, el 46,9% presentó ≥ 1 visita a urgencias (total: 50 consultas). Tras el cambio por budesonida/formoterol, el 21% requirió al menos una visita a urgencias (total: 14 consultas; p < 0,01). La proporción de pacientes con ≥ 2 consultas a urgencias fue de 19,7% con el tratamiento basal y de 1,6% tras el cambio a budesonida/formoterol (p < 0,01). No se observaron diferencias significativas en la cantidad de hospitalizaciones. En este estudio del mundo real de pacientes con asma moderada a grave, el cambio del tratamiento a budesonida/formoterol se asoció con reducción significativa de las consultas a urgencias, a pesar de no detectarse cambios de significación estadística en los índices espirométricos habituales.

Asthma is characterized by its deleterious impact, including a high cost to the healthcare system. In patients with poorly controlled asthma despite treatment, a maintenance regimen of inhaled corticosteroids and formoterol is proposed. The aim of this retrospective, observational study was to evaluate the spirometric changes after switching the controller medication in patients with moderate to severe asthma attended in our institution ("Hospital Clínico de Magallanes"), as well as the variation in the number of severe exacerbations (consultation to an emergency department and/or hospitalization for asthma). Sixty-one adults with moderate to severe asthma (median age: 60 years-old [range: 21-87], women: 69.4%; atopic/allergic comorbidity: 79%; other comorbidities: 46.8%) in whom treatment with fluticasone/salmeterol 250/25 μg was switched to budesonide/formoterol 160/4.5 μg participated in our study. No significant changes in spirometric parameters were observed after the replacement treatment. With the initial treatment, 46.9% patients presented ≥ 1 visit to the emergency department (total: 50 visits). After the switch to budesonide/formoterol, 21% required at least one emergency department visit (total: 14 consultations; p < 0.01). The proportion of patients with ≥ 2 emergency department visits was 19.7% with baseline treatment and 1.6% after switching to budesonide/formoterol (p < 0.01). No significant differences were observed in the number of hospitalizations. In this real-world study of moderate to severe asthma patients, switching to budesonide/formoterol was associated with a significant reduction in emergency department visits, despite no statistically significant changes in the usual spirometric parameters.

Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD).@*METHODS@#A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks.@*RESULTS@#Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P<0.05). Compared with the conventional treatment group, the observation group had a significantly lower fraction of inspired oxygen at 24 and 48 hours and 3, 7, and 21 days after administration, significantly shorter durations of invasive ventilation, noninvasive ventilation, ventilator application, and oxygen therapy, a significantly lower incidence rate of BPD, and a significantly lower severity of BPD (P<0.05). There was no significant difference in the incidence rate of glucocorticoid-related complications between the two groups (P>0.05).@*CONCLUSIONS@#Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

Rinosinusitis micótica alérgica con destrucción de base de cráneo / Allergic fungal rhinosinusitis with skull base destruction

La sinusitis micótica alérgica es una enfermedad inflamatoria de la mucosa rinosinusal producida por hongos que pueden aislarse de la cavidad de nasal de individuos sanos. Se produce indirectamente por los hongos que actúan como antígeno y desencadenan una reacción inmunológica mediada por IgE que origina pólipos y una secreción mucosa espesa con detritus e hifas denominada mucina. Su presentación clínica más frecuente es una sinusitis crónica unilateral o bilateral con pólipos. Con menos frecuencia, las sustancias originadas por la desgranulación de los eosinófilos producen remodelación o destrucción ósea y la sinusitis puede simular una neoplasia. Se describe el caso clínico de un paciente que padeció una sinusitis micótica alérgica con destrucción ósea masiva de la base del cráneo y que tuvo extensión intracraneal extradural e intraorbitaria de la enfermedad. Fue tratado con éxito mediante cirugía y corticoides. (AU)

Allergic fungal sinusitis is an inflammatory disease of the rhinosinusal mucosa caused by fungi that can be isolated from the nasal cavity of healthy individuals. The pathology is produced indirectly by the fungus that acts as an antigen and triggers an IgE-mediated allergic reaction that causes polyps and a thick mucous discharge with detritus and hyphae called mucin. Its most common clinical presentation is unilateral or bilateral chronic sinusitis with polyps. Less commonly, substances originated by the degranulation of eosinophils cause bone remodeling or destruction, and sinusitis can simulate a neoplasia. We describe the clinical case of a patient who suffered from allergic fungal sinusitis with massive bone destruction of the skull base and who had intracranial, extradural and intraorbital extension of the disease. He was successfully treated with surgery and corticosteroids.Key words: allergic fungal sinusitis, intracranial extension, endoscopic surgery, transorbital transpalpebral approach. (AU)

Actualizaciones basadas en evidencia COVID-19 Budesonide inhalado para el tratamiento de pacientes en COVID-19 / Evidence-based updates COVID-19 Inhaled budesonide for the treatment of patients in COVID-19

La enfermedad por el Coronavirus 2019 (COVID-19 - Coronavirus Disease 2019) es una patología respiratoria de humanos producida por la infección por un nuevo coronavirus identificado con la sigla SARS-CoV-2.1 El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaró al COVID-19 como una pandemia, y desde ese momento hasta el 13 mayo del 2021 se ha reportado aproximadamente para Argentina con más de 3.000.000 casos confirmados y 68.807 muertes.1,2 Al no existir un tratamiento farmacológico específico contra el virus hasta el momento (aunque esteroides sistémicos han demostrado reducir la mortalidad en pacientes hospitalizados por COVID-19 con complicaciones respiratorias graves y que las heparinas son efectivas en la prevención de la trombosis venosa profunda también en casos graves), la comunidad científica se ha enfocado en la búsqueda y desarrollo de intervenciones antivirales, y en resignificar diferentes tipos de fármacos que se utilizan en otras indicaciones. El presente informe pretende evaluar si el empleo de budesonide inhalado es eficaz, seguro y resulta conveniente para el tratamiento de pacientes con COVID-19 en Argentina

Budesonide inhalado para el tratamiento de pacientes con COVID-19 / Inhaled budesonide for treating COVID-19 patients

INTRODUCCIÓN: En los primeros informes de China, Italia y Estados Unidos que describen a los pacientes con COVID-19 ingresados en el hospital, los pacientes con asma y enfermedad pulmonar obstructiva crónica (EPOC) estaban significativamente sub-representados.3-6 Surgió entonces la hipótesis que esta subrepresentación de las primeras cohortes, podría deberse al uso generalizado de glucocorticoides inhalados en esta población. 7 El uso de glucocorticoides inhalados en pacientes con asma y EPOC tiene la finalidad de disminuir la inflamación de las vías aéreas y de este modo contribuir a reducir las exacerbaciones, que a menudo se deben a infecciones de origen viral. 8 Los estudios in vitro han demostrado que los glucocorticoides inhalados reducen la replicación de SARS-CoV-2 en las células epiteliales de las vías respiratorias, además de la regulación en menos de la expresión de los genera ACE2 y TMPRSS2, que son críticos para la entrada de células virales en este epitelio.9 Budesonide inhalado se encuentran ampliamente disponible en Argentina y está aprobada por la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) para la prevención de los síntomas respiratorios relacionados con la inflamación bronquial aguda o crónica. Se realizó una evaluación de tecnología sanitaria, basada en evidencia proveniente de revisiones sistemáticas vivas y guías de práctica clínica de alta calidad metodológica para brindar parámetros actualizados y balanceados que sean de utilidad para la toma de decisiones en los diferentes niveles de gestión. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del uso de esteroides inhalados para el tratamiento de pacientes con COVID-19. MÉTODOS: Efectos en la Salud: Se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma Love de Epistemonikos para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente.10 De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos separando los efectos del tratamiento sobre pacientes con COVID-19 (mortalidad, ingreso en asistencia ventilatoria mecánica, duración de estadía hospitalaria, tiempo a la resolución de síntomas o mejoría clínica al día 7-28 y eventos adversos graves) y la certeza en dichos efectos. Adicionalmente se extractaron datos relacionados a efectos de subgrupo potencialmente relevantes para la toma de decisión, con especial énfasis en el tiempo de evolución y la severidad de la enfermedad. Implementación: Este domino contempla dos subdominios: la existencia de barreras y facilitadores para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Recomendaciones: se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: Efectos en la Salud: Se identificaron dos revisiones sistemáticas que cumplen con los criterios de inclusión del presente informe y que reportan sobre budesonide inhalado para pacientes con COVID-19. Se identificaron 2 ECA que incluyeron 1929 participantes en los que budesonide inhalado se comparó con la atención estándar u otros tratamientos. CONCLUSIONES: El cuerpo de evidencia disponible hasta el momento sugiere que budesonide inhalado podría mejorar el tiempo de resolución de los síntomas y disminuir las hospitalizaciones. Existe incertidumbre en el efecto de budesonide inhalado sobre la mortalidad, los efectos advsersos severos o el ingreso en asistencia ventilatoria mecánica. Budesonide inhalado se encuentran ampliamente disponible en Argentina y está aprobada por ANMAT para el tratamiento de síntomas respiratorios relacionados con la inflamación bronquial aguda o crónica. Su costo comparativo es bajo y no se identificaron recomendaciones que aborden el uso de esteroides inhalados para el tratamiento de COVID-19.

Refractory celiac disease type 2: how to diagnose and treat?

SUMMARY Refractory celiac disease is an uncommon condition which might be associated to poor prognosis. It is often treated with immunosuppressive medications, with poor results. It is divided in type 1 and type 2, the latter carrying a high risk for lymphoma and mortality. A case of a 41 year old female patient with refractory celiac disease type 2 is reported. She was treated with oral budesonide for six months, achieving histological remission.

Características clínicas e fatores associados à asma grave em Salvador, Brasil / Clinical features and associated factors with severe asthma in Salvador, Brazil

RESUMO Objetivo Descrever características clínicas e identificar fatores associados a maior gravidade da asma, em uma amostra de pacientes acompanhados em um centro de referência em Salvador. Métodos Estudo transversal de 473 adultos, acompanhados regularmente no Programa para Controle da Asma na Bahia (ProAR), reavaliados de forma sistemática entre 2013 e 2015. Os pacientes foram admitidos por preencher critérios anteriores de asma grave e reclassificados de acordo com a definição mais atual, proposta por um documento conjunto da European Respiratory Society/American Thoracic Society (ERS/ATS 2014). Resultados Foram reclassificados como portadores de asma grave pelos critérios da ATS/ERS (AG-ERS/ATS) 88/473 (18%). Destes, 87% eram mulheres, 48% obesos, com mediana do índice de massa corporal (IMC) de 29 kg/m2 (IQ 26-34), 99% tinham sintomas de rinite crônica e 83%, sintomas de doença do refluxo gastroesofágico (DRGE). Nenhum se declarou fumante atual. Os principais corticosteroides inalatórios utilizados foram beclometasona (88%) e budesonida (69%). A maioria relatou adequada adesão (77%) e a minoria das avaliações (0,6%) revelou erros graves na técnica inalatória. A mediana do volume expiratório forçado no primeiro segundo pós-broncodilatador (VEF1pós-BD) foi 67% do predito (IQ 55-80). A mediana do número de eosinófilos no sangue periférico foi menor nos pacientes com AG-ERS/ATS [209 células/mm3 (IQ 116-321)] do que nos demais pacientes estudados [258 células/mm3 (IQ 154-403)]. Sintomas de doença do refluxo gastroesofágico (DRGE) foram associados a mais gravidade [OR = 2,2; IC95% (1,2-4,2)]. Conclusões Neste grupo de pacientes, sintomas de RGE foram associados a AG-ERS/ATS e contagem de eosinófilos > 260 células/mm3 esteve associada a 42% menos chance de AG-ERS/ATS.

ABSTRACT Objective To describe the clinical features and to identify factors associated with significant severe asthma in samples of patients followed in a reference center in Salvador. Methods A cross-sectional study of 473 adults, regularly followed in the "Asthma Control Program" in Bahia (Programa de Controle da Asma e da Rinite Alérgica na Bahia (ProAR)), reassessed systematically between 2013 and 2015. The patients were admitted for meeting previous criteria of severe asthma and were reclassified according to the most current definition proposed by a joint document of the "European Respiratory Society/American Thoracic Society" (ERS/ATS) (ERS/ATS 2014). Results Only 88/473 (18%) were reclassified as having severe asthma by ERS/ATS criteria (SA-ERS/ATS). Among these patients, 87% were women, 48% obese, with a median Body Mass Index (BMI) of 29 kg·m2 (IQ 26-34), furthermore, 99% had symptoms of chronic rhinitis and 83% had symptoms of Gastroesophageal Reflux Disease (GERD). None of the 88 patients claimed to be current smokers. The most frequently corticosteroids were beclomethasone dipropionate (BDP) (88%) and budesonide (BUD) (69%). The majority of the evaluations reported adequate adherence (77%), however, the minority (0,6%) detected serious errors in inhalation techniques. The median Forced Expiratory Volume (FEV1) associated with post-bronchodilator test (post-BD) was 67% predicted (IQ 55-80). The median number of eosinophils in the peripheral blood was lower in patients with SA-ERS/ATS (258 cells/mm3 (IQ 116-321) than in the other patients studied [258 cells/mm3 (IQ 154-403)]. Gastroesophageal reflux symptoms were associated with a higher severity [OR = 2.2 95% CI (1.2-4.2)]. Conclusion In this group of patients, symptoms of GERD were associated with SA-ERS/ATS and eosinophil count > 260 cells/mm3 were associated 42% with less chance SA-ERS/ATS

Clinical observation of herb-separated moxibustion combining western medication on allergic rhinitis of kidney- deficiency type and correlation with infrared thermal imagining / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of herb-separated moxibustion combined with budesonide nasal spray (rhinocort) on moderate to severe persistent allergic rhinitis (AR) of kidney- deficiency type, and to explore the correlation between nasal temperature and condition of allergic rhinitis.@*METHODS@#A total of 70 patients with moderate to severe persistent AR were randomized into an observation group (35 cases) and a control group (35 cases, 3 cases dropped off). Both groups were treated with rhinocort, one spray on each side of the nostril (approximately 64 μg each spray), once in the morning and once in the evening, for 4 weeks. On the basis of the above treatment, the observation group was treated with herb-separated moxibustion at Shenshu (BL 23), Feishu (BL 13), Zhiyang (GV 9), Dazhui (GV 14), 3 moxibustions per acupoint, a single treatment lasting about 30 min. This treatment was given once every other day, 3 times every week, and totally continuous 4 weeks. The changes of AR symptom visual analogue scale (VAS) scores were observed before and after treatment and at 3 months follow-up after treatment. The heat variation (temperature, range) on projection areas of the nose, lungs, large intestine and kidneys of the two groups' patients before and after treatment were detected by the infrared thermal imaging diagnostic system, and the correlation between the VAS scores and nasal temperature before and after treatment was analyzed. The clinical effects of both groups were evaluated according to the VAS score.@*RESULTS@#The total effective rate in the observation group after treatment was 85.7% (30/35), which was higher than 71.9% in the control group (23/32, <0.05). After treatment and at follow-up, the VAS scores of both groups were lower than those before treatment (<0.05), and the VAS score of the observation group was lower than that of the control group at follow-up (<0.05). After treatment, the nasal temperature, pulmonary range, large intestinal range and renal range of the observation group were all lower than those before treatment (<0.05), the nasal temperature and nasal range of the control group were lower than before treatment (<0.05), and the reduction of nasal temperature, nasal range and renal range in the observation group was greater than that of the control group (<0.05). Before and after treatment, there was a correlation between VAS score and nasal temperature (<0.05).@*CONCLUSION@#The herb-separated moxibustion combining western medication has a better effect and long-term effect than western medication alone for moderate to severe persistent AR, which can improve heat variation on projected areas of the nose, lung, large intestine and kidney of patients. In addition, nasal temperature can reflect the severity of the symptoms of patients with moderate to severe persistent AR, or it can be used as a secondary indicator to evaluate condition of AR.

Particulate Matter 2.5 Causes Deficiency in Barrier Integrity in Human Nasal Epithelial Cells

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.

Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment

PURPOSE: We evaluated the severity of olfactory disturbance (OD) in the murine model of allergic rhinitis (AR) and local allergic rhinitis (LAR) in mice. We also investigated the therapeutic effect of an intranasal steroid on OD. METHODS: Forty BALB/c mice were divided into 5 groups (n = 8 for each). The control group was sensitized intraperitoneally (i.p.) and challenged intranasally (i.n.) with saline. Mice in the AR group got i.p. and i.n. ovalbumin (OVA) administration for AR induction. The LAR group was challenged i.n. with 1% OVA for inducing local nasal allergic inflammation, without inducing the systemic allergy. The OD group got an i.p. methimazole administration (75 mg/kg) to induce total destruction of olfactory mucosa. Mice in the intranasal budesonide group received i.n. budesonide (12.8 μg per time, 30 minutes after the i.n. OVA challenge) while using OVA to cause systemic allergies. We conducted a buried-food pellet test to functionally assess the degree of OD in each group by measuring the time taken until finding hidden food. We evaluated the damage to olfactory epithelium using histopathologic evaluation and compared the degree of olfactory marker protein (OMP) expression in olfactory epithelium using immunofluorescent staining. RESULTS: Mice of the AR (81.3 ± 19.8 seconds) and LAR groups (66.2 ± 12.7 seconds) spent significantly more time to detect the pellets than the control group (35.6 ± 12.2 seconds, P < 0.01). After treatment, the intranasal budesonide group exhibited significantly better results (35.8 ± 11.9 seconds) compared with the AR and LAR groups (P < 0.01). The AR and LAR groups showed considerable olfactory epithelial damage and suppression of OMP expression compared with the control group. In the intranasal budesonide group, the olfactory lesions and OMP expression had improved substantially. CONCLUSIONS: OD may be caused by olfactory epithelial damage and suppression of OMP expression in nasal allergic inflammation and could be reversed using an intranasal steroid.

Effect of intermittent versus daily inhalation of budesonide on pulmonary function and fractional exhaled nitric oxide in children with mild persistent asthma / 中国当代儿科杂志

OBJECTIVE@#To study the effect of intermittent versus daily inhalation of budesonide on pulmonary function and fractional exhaled nitric oxide (FeNO) in children with mild persistent asthma.@*METHODS@#A total of 120 children, aged 6-14 years, with mild persistent asthma who attended the hospital from January 2016 to January 2018 were enrolled. The children were divided into an intermittent inhalation group with 60 children (inhalation of budesonide 200 μg/day for 6 weeks when symptoms of asthma appeared) and a daily inhalation group with 60 children (continuous inhalation of budesonide 200 μg/day) by stratified randomization. The children were followed up at months 3, 6, 9, and 12 of treatment. The two groups were compared in terms of baseline data, changes in FeNO and pulmonary function parameters, amount of glucocorticoid used, number of asthma attacks, and asthma control.@*RESULTS@#At the start of treatment, there were no significant differences in baseline data, FeNO, and pulmonary function between the two groups (P>0.05). Over the time of treatment, FeNO gradually decreased and pulmonary function parameters were gradually improved in both groups (P0.05). Compared with the daily inhalation group, the intermittent inhalation group had a significantly lower amount of budesonide inhaled (P<0.05) and a significantly higher number of asthma attacks (P<0.05).@*CONCLUSIONS@#Intermittent inhalation and daily inhalation of budesonide can achieve the same level of asthma control in children with mild persistent asthma and both have no influence on the increases in body height and body weight. Daily inhalation of budesonide can produce a better efficiency in reduing FeNO and increasing FEV1%pred. Although intermittent inhalation can reduce the amount of glucocorticoid used, it may lead to a higher risk of asthma attacks.

Uso de corticoide inalado e sua implicação no nível de eosinófilos periféricos / Inhaled corticosteroid use and its implications for peripheral blood eosinophil levels

Introdução: Um dos efeitos do corticoide sistêmico é a redução do número e da ação dos eosinófilos. O objetivo deste estudo foi avaliar a ação do corticoide inalatório (CI) sobre os eosinófilos periféricos (EoP). Métodos: Trata-se de um estudo retrospectivo de prontuários eletrônicos de pacientes adultos com asma grave, steps 4 e 5 da GINA 2019, acompanhados em um centro terciário de referência. Os pacientes em uso recente ou atual de corticoide oral foram excluídos. Foram avaliados dados demográficos, dose de budesonida inalada, sensibilização a aeroalérgenos, IgE total, cortisol sérico e EoP, no período de 2010 a 2019. Resultados: Foram avaliados 58 pacientes, sendo 81,0% do sexo feminino, com médias de idade de 61,0 anos, de início da asma aos 17,4 anos e de tempo de doença de 43,6 anos. A média de CI foi de 1682,8 µg/dia, e a média de IgE sérica total do grupo foi de 398,9 UI/mL. A IgE específica para aeroalérgenos estava positiva em 40 pacientes (69%), sendo 85% destes pacientes sensibilizados para ácaros. A média do cortisol sérico foi de 5,6 µg/dL, e dos EoP de 252,1 cel/mm3. Neste estudo não foi observada correlação entre a dose de CI e o cortisol sérico. Entretanto, 41,4% dos pacientes apresentaram EoP < 150 cel/mm3, e houve uma correlação inversa significante entre as doses de CI e os níveis de EoP, (p = 0,011 r2 = 0,11), ou seja, quanto maior a dose de CI, menor o nível de EoP. Conclusões: A GINA 2019 recomenda o uso de anticorpos monoclonais (mAbs), no step 5, direcionados pelo fenótipo de asma. Alguns destes mAbs incluem como critério de tratamento os EoP acima de 150 ou 300 cel/mm³. Neste estudo, o CI em doses elevadas estava relacionado a níveis mais baixos de EoP, portanto, alguns pacientes em uso de doses elevadas de CI poderiam apresentar EoP reduzida pelo uso de CI, interferindo na recomendação de alguns mAbs.

Introduction: One of the effects of systemic corticosteroids is to reduce the number and action of eosinophils. The aim of this study was to evaluate the action of inhaled corticosteroids (ICS) on peripheral blood eosinophils (PBE). Methods: We retrospectively reviewed the medical records of adult patients with severe asthma, steps 4-5 (GINA 2019), treated at a tertiary referral center. Patients on current or recent oral corticosteroid therapy were excluded. Data on demographics, ICS dose, sensitization to aeroallergens, total serum IgE, serum cortisol, and PBE counts were evaluated for the period from 2010 to 2019. Results: Fifty-eight patients were evaluated, 81% were women. Mean age was 61 years, with the onset of asthma at 17.4 years of age and disease duration of 43.6 years. The mean ICS dose was 1682.8 µg/day, and the mean total serum IgE was 398.9 IU/mL. Specific IgE for aeroallergens was positive in 40 patients (69%); of these, 85% were sensitized to mites. The mean serum cortisol level was 5.6 µg/dL, and the mean PBE count was 252.1 cells/mm3. There was no correlation between ICS dose and serum cortisol, but 41.4% of patients had PBE counts <150 cells/mm3. There was a significant inverse correlation between ICS doses and PBE counts (p=0.011, r2=0.11), i.e., the higher the ICS dose, the lower the PBE count. Conclusions: GINA 2019 recommends the use of monoclonal antibodies (mAbs) in asthma step 5, directed by phenotype. Some of these mAbs have as a treatment criterion PBE count above 150 or above 300 cells/mm3. In this study, high-dose ICS was correlated with lower PBE levels. Therefore, patients using high-dose ICSs could have their PBE levels reduced by ICS use, interfering with the recommendation of some mAbs.

Monitoramento prospectivo do uso de medicamentos: lesão hepática induzida por medicamentos em um centro municipal de saúde / Prospective monitoring of drug use: drug-induced liver injury in a primary healthcare center

ABSTRACT BACKGROUND: Drug-induced liver injury is still misunderstood in Brazil due to diagnostic difficulties or lack of reporting incidents. OBJECTIVE: To assess the frequency of adverse events related to the use of medicines in a primary healthcare unit, in a city locate southwestern of the state of Bahia, Brazil. METHODS: Prospective study conducted at the Primary Center for Specialized Health (CEMEA), February at August of 2013 in Vitoria da Conquista, Bahia, Brazil. Interviews were conducted with patients over 18 years old, and their clinical and laboratorial data were collected. The CIOMS scale was used to validate the cases. RESULTS: A total of 149 patients, mainly Afro-Brazilian women, received follow-up. Among these patients, three cases of hepatotoxicity were identified, and the medicines associated to drug-induced liver injuries were: nimesulide, budesonide and valacyclovir. CONCLUSION: Drug-induced liver injury is rare in primary healthcare units. It also allowed estimating the incidence of hepatotoxicity induced by allopathic medicines which are standardized by public healthcare authorities.

RESUMO CONTEXTO: As lesões hepáticas induzidas por drogas (DILI), ainda são mal compreendidas no Brasil devido a dificuldades diagnósticas ou à falta de relatos. OBJETIVO: Avaliar a frequência de eventos adversos relacionados ao uso de medicamentos em uma unidade básica de saúde, em uma cidade do sudoeste baiano. MÉTODOS: Estudo prospectivo realizado no período de fevereiro a agosto de 2013 em Vitória da Conquista, Bahia, Brasil. Entrevistas foram realizadas com pacientes maiores de 18 anos; os dados clínicos e laboratoriais foram coletados. A escala do CIOMS foi usada para avaliar causalidade dos casos. RESULTADOS: Um total de 149 pacientes, principalmente mulheres afro-brasileiras, receberam acompanhamento. Entre esses pacientes, três casos de hepatotoxicidade foram identificados e os medicamentos associados à DILI foram: nimesulida, budesonida e valaciclovir. CONCLUSÃO: DILI é raro em unidades básicas de saúde. Os três casos foram todos reversíveis, sem necessidade de internação hospitalar. Políticas de saúde que fomentam a prática da farmacovigilância são extremamente importantes para a prevenção e detecção de DILI.

Dermatite de contato por corticoide em pacientes com dermatite atópica / Corticosteroid contact dermatitis in patients with atopic dermatitis

Objetivo: Avaliar a sensibilização a corticoides tópicos e substâncias do teste de contato padrão e cosméticos em pacientes com dermatite atópica (DA) no Serviço de Alergia e Imunologia do HSPE-SP. Método: Estudo retrospectivo com análise de prontuário de pacientes com DA, classificados de acordo com o SCORing Atopic Dermatitis (SCORAD) em leve, moderada e grave, que foram atendidos no ambulatório de Alergia e Imunologia do HSPE-SP, submetidos a teste de contato com baterias padrão, cosméticos, corticoides, incluindo furoato de mometasona. Resultados: Após análise estatística dos dados de 51 pacientes portadores de DA, foi identificada maior prevalência no gênero feminino (73%). Pacientes com DA moderada/grave apresentaram maior positividade (62%) para pelo menos uma substância. Foram mais propensos a positivar para teste de contato, pacientes maiores de 18 anos. As substâncias que foram mais positivas na bateria padrão foram: sulfato de níquel (33%), neomicina (10%), e bicromato de potássio e cloreto de cobalto (8% cada). O sulfato de níquel foi mais positivo no gênero feminino. Três (5,9%) pacientes apresentaram positividade para teste de contato com bateria de corticoides, sendo positivas substâncias betametasona 1%, budesonida 0,01% e butirato de hidrocortisona 1%, e todos eram portadores de DA leve. Foi identificada relação entre positividade para bateria de corticoides e sulfato de níquel. Conclusão: Os testes de contato foram mais positivos em adultos. Houve maior sensibilidade para o sulfato de níquel no gênero feminino. Sensibilidade importante à neomicina na DA moderada/grave. Pacientes com alergia de contato por corticoides podem apresentar alergia a sulfato de níquel. Esse trabalho chama atenção para a porcentagem importante de pacientes com DA acometidos por alergia de contato por corticoides, sendo esse tipo alergia um problema emergente e que tem sido cada vez mais relatado na última década; porém, ainda são escassos os estudos envolvendo esse assunto.

Objective: To evaluate sensitization to topical corticosteroids and standard patch testing substances in patients with atopic dermatitis (AD) at the HSPE-SP Allergy and Immunology Department. Methods: This retrospective study assessed medical records of patients with AD, whose severity was classified as mild, moderate or severe according to SCORing Atopic Dermatitis (SCORAD). They were seen at the HSPE-SP Allergy and Immunology outpatient clinic and underwent a patch test with the following series: standard, cosmetics, and corticosteroids, including mometasone furoate. Results: After statistical analysis of data from 51 patients with AD, a higher prevalence was identified in female participants (73%). Patients with moderate-to-severe AD had more positive results (62%) for at least one substance. Patients older than 18 years were more likely to be positive in the patch test. The substances that were most frequently positive in the standard series were nickel sulfate (33%), neomycin (10%) and potassium dichromate and cobalt chloride (8% each). Positive nickel sulfate was more common in female participants. Three (5.9%) patients were positive for corticosteroids (1% betamethasone, 0.01% budesonide and 1% hydrocortisone butyrate) and all had mild AD. A relationship between positivity for corticosteroid series and nickel sulfate was identified. Conclusion: Patch tests were more frequently positive in adults. There was higher sensitivity to nickel sulfate in female patients. There was important sensitivity to neomycin in patients with moderate-to-severe AD. Patients with corticosteroid contact allergy may present with allergy to nickel sulfate. This paper draws attention to the important percentage of patients with AD affected by corticosteroid contact allergy, which has become an emerging problem that has been increasingly reported in the past decade. However, there are still few studies addressing this topic.

Eficacia de la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar de personas mayores con Enfermedad Pulmonar Obstructiva Crónica: revisión sistemática de literatura / Effectiveness of budesonide/formoterol compared to fluticasone / salmeterol in improving the lung capacity of older people with Chronic Obstructive Pulmonary Disease: systematic literature review / Eficiência da budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar de idosos com Doença Pulmonar Obstrutiva Crônica: revisão sistemática da literatura

Introducción. La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una patología no transmisible, caracterizada por una limitación de flujo de aire en las vías respiratorias debido a una respuesta inmunológica anormal frente a partículas. Objetivo. Conocer la eficacia que tiene la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar en personas mayores de 40 años con Enfermedad Pulmonar Obstructiva Crónica. Materiales y métodos. Se realizó una revisión sistemática de documentos producidos entre el año 2000 y 2018 en distintas bases de datos, donde se incluyeron ensayos clínicos. Se identificaron cuatro artículos para el análisis final. Resultados. Durante la evaluación comparativa de budesonida con formoterol, los artículos muestran un total de 709 personas evaluadas, con un promedio de edad de 53,5 años. El 65,4 % eran varones, el 21 % manifestaba no haber consumido tabaco, todos con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica moderada-severa, según la escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Los estudios determinaron que al administrar budesonida/formoterol de 400/12 mcg y 320/9 mcg, los pacientes tuvieron una leve mejoría en el Volumen Espiratorio Forzado del primer segundo (VEF1). Solo dos pacientes presentaron efectos adversos. No obstante, para los resultados mencionados anteriormente no se encontró diferencias significativas. Conclusiones. El uso de budesonida/formoterol es eficaz al mejorar la capacidad ventilatoria pulmonar, disminuye el número de exacerbaciones anuales y genera un adecuado control de los síntomas, sin embargo, es igual de efectivo a la fluticasona/salmeterol.

Introduction. Chronic Obstructive Pulmonary Disease (COPD) is a not transmissible disease, characterized by a limitation of airflow in the respiratory tract, due to an abnormal immune response to particles. Objective. This article aims to show that the application of budesonide / formoterol improves lung capacity in people over 40 years with Chronic Obstructive Pulmonary Disease. Materials and methods. A systematic review was conducted in the period between 2000 and 2018 in different databases where clinical trials were included. Four articles were identified for the final analysis. Results. During the comparative evaluation of budesonide with formoterol, a total of 709 people were evaluated, with an average age of 53.5 years, 65.4% were male, 21% reported not having used tobacco, all with a diagnosis of moderate-severe Chronic Obstructive Pulmonary Disease according to the GOLD scale (Global Initiative For Chronic Obstrutive Lung Disease). The studies determined that when budesonide / formoterol of 400/12 mcg and 320/9 mcg was administered, the patients had a slight improvement in the Forced Expiratory Volume of the first second (FEV1). Only two patients presented adverse effects. However, for the results mentioned above no significant differences were found. Conclusions. The use of budesonide / formoterol is effective in improving pulmonary ventilatory capacity, decreases the number of annual exacerbations and generates adequate control of symptoms, however, it is equally effective in fluticasone / salmeterol.

Introdução. A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma patologia não transmissível, caraterizada por uma limitação do fluxo de ar nas vias aéreas devido a uma resposta imune anormal contra partículas. Objetivo. Conhecer a eficiência que apresenta a budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar em pessoas com mais de 40 anos com Doença Pulmonar Obstrutiva Crônica. Materiais e métodos. Foi realizada uma revisão sistemática dos documentos produzidos entre 2000 e 2018 em diferentes bancos de dados, onde foram incluídos ensaios clínicos. Quatro artigos foram identificados para a análise final. Resultados. Durante a avaliação comparativa de budesonida com formoterol, os artículos mostram um total de 709 pessoas avaliadas, com uma idade média de 53,5 anos. O 65,4 % eram do sexo masculino, o 21 % disseram que não usavam tabaco, todos diagnosticados com Doença Pulmonar Obstrutiva Crônica moderada a grave, de acordo com a escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Os estudos determinaram que administrar budesonida/formoterol de 400/12 mcg e 320/9 mcg, os pacientes apresentaram uma leve melhora no Volume Expiratório Forçado no primeiro segundo (VEF1). Apenas dois pacientes tiveram efeitos adversos. No entanto, não foram encontradas diferenças significativas para os resultados mencionados acima. Conclusões. O uso de budesonida/formoterol é eficaz na melhora da capacidade ventilatória pulmonar, diminui o numero de exacerbações anuais e gera controle adequado dos sintomas, no entanto, é igualmente eficaz para a fluticasona/salmeterol.

Diagnóstico y manejo de la colitis microscópica / Diagnosis and management of microscopic colitis

Microscopic colitis (MC) is a clinical condition characterized by chronic watery diarrhea, normal colonic mucosa and characteristic histological findings. It is composed of two main entities: collagenous colitis (CC) and lymphocytic colitis (LC). Its incidence has been increasing, currently accounting for between 8 to 16% of studies for chronic diarrhea. It is more frequent in elderly women and is strongly associated with other autoimmune disorders. Its pathogenesis is not very well understood, but it supposes the immune activation secondary to the exposure of the colonic mucosa to different luminal antigens, mainly drugs. Management includes suspension of the potential causative agent and the use of anti-diarrheal medications. Oral budesonide has proven to be effective in induction and maintenance of remission, but with a high rate of recurrence upon discontinuation. Immune-modulators drugs such as azatioprine and metrotrexate have been tested in patients dependent to corticoids with variable results. Antibodies against tumor necrosis factors (TNF) are under studies, with promising results.

La colitis microscópica (CM) es una condición clínica caracterizada por diarrea crónica acuosa con mucosa colónica normal y hallazgos histológicos característicos. Está compuesta por dos entidades principales: la colitis colágena (CC) y la colitis linfocítica (CL). Su incidencia ha ido en aumento, siendo en la actualidad la responsable del 8 a 16% de los casos por diarrea crónica. Es más frecuente en mujeres de edad avanzada con una fuerte asociación a otras enfermedades autoinmunes. Su etiopatogenia no es del todo conocida, pero se cree juega un rol la activación inmune secundaria a la exposición de la mucosa colónica a diferentes antígenos luminales, principalmente fármacos. Dentro del manejo se incluye la suspensión del potencial agente causal y el uso de fármacos antidiarreicos. La budesonida oral ha demostrado alta efectividad en la inducción y mantención de la remisión, pero con una alta tasa de recurrencia al suspenderla. Fármacos inmunomoduladores como azatioprina y metrotrexato se han probado en pacientes corticodependendientes con resultados variables. El uso de anticuerpos monoclonales anti factor de necrosis tumoral (TNF) se encuentra en estudio, con resultados prometedores.

Astragalus membranaceus improves therapeutic efficacy of asthmatic children by regulating the balance of Treg/Th17 cells / 中国天然药物

Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group (control group, the combination of budesonide and terbutaline) and A. membranaceus group (treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy. Porcine peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of FoxP3, EGF-β, IL-17 and IL-23 from PBMCs and serum IgE were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group (P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group (P < 0.05). The levels of IgE, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group (P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.