Guia Prático de Atualização no tratamento da exacerbação de asma na criança e no adolescente ­ Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical Update Guide on the treatment of asthma exacerbation in children and adolescents ­ Joint position of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.

Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.

Beta-2 agonistas para el tratamiento de bronquiolitis / Beta-2 agonists for the treatment of bronchiolitis

INTRODUCCIÓN La bronquiolitis es la inflamación aguda de las vías aéreas de pequeño calibre, teniendo como causa principal las infecciones virales. Es altamente frecuente en menores de dos años, sobretodo en menores de 12 meses. Existe gran controversia sobre el manejo de esta patología, siendo especialmente cuestionable el uso de beta-2 agonistas de corta acción tanto en el ámbito ambulatorio como hospitalario. MÉTODOS Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos siete revisiones sistemáticas que en conjunto incluyen 47 estudios primarios, de los cuales 44 corresponden a ensayos aleatorizados. Concluimos que el uso de beta-2 agonistas podría no tener ningún beneficio en el manejo de la bronquiolitis, en términos de necesidad de hospitalización y/o duración de la misma. Por otra parte, podría aumentar efectos adversos como arritmias, sin embargo, la certeza de esta evidencia es baja

Asma grave em pacientes adultos e pediátricos: Protocolo da Sociedade Mineira de Pneumologia e Cirurgia Torácica (SMPCT) - 2019 / Severe asthma in adult and pediatric patients: Protocol of the Sociedade Mineira de Pneumologia e Cirurgia Torácica (SMPCT) - 2019

Este documento é uma revisão do protocolo de asma grave da SMPCT de 2015, que se fez necessária devido à atualização de avanços em pesquisas, principalmente em fenotipagem/genotipagem e terapêutica da asma grave, além de asma grave na pediatria. A maioria da publicações relata que 5% a 10% dos asmáticos podem apresentar asma grave. Porém, levantamento na Holanda encontrou uma prevalência menor, de 3,6% ou 10,4/10000 habitantes, que parece ser mais próximo da realidade. Este protocolo tem como população alvo os pacientes com asma grave, adultos e pediátricos, conforme definições de asma grave da"International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma" de 2014 e GINA 2018.1,3 Seus potenciais utilizadores são especialistas em doenças respiratórias que lidam com asma grave, e que devem ser os responsáveis pela aplicação do protocolo, e também clínicos gerais, pediatras, médicos de cuidados primários, enfermeiros, fisioterapeutas e outros profissionais da saúde. É aconselhável consulta com um especialista em asma nos seguintes casos: asma de difícil diagnóstico, suspeita de asma ocupacional, asma persistente não controlada com exacerbações frequentes, asma com risco de morte, eventos adversos significativos ou suspeita de subtipos de asma grave.4 Este documento não tem a intenção de instituir um tratamento padronizado, mas estabelecer bases racionais para decisões em pacientes com asma grave, pois as recomendações não conseguem abranger toda a complexidade do julgamento clínico em casos individuais. Os autores recomendam sua revisão e atualização no período máximo de 3 anos, ou, se necessário, em tempo menor.

Mioclonías inducidas por salbutamol / Myoclonus induced by salbutamol: A case report

Resumen El salbutamol es un agonista adrenérgico β2 ampliamente empleado en pacientes con enfermedades pulmonares obstructivas y restrictivas. Sus principales efectos secundarios son la taquicardia y el temblor. Las mioclonías son contracciones musculares involuntarias, irregulares, bruscas, breves y repentinas, y pueden ser generalizadas, focales o multifocales. Se presenta el caso de un paciente de 61 años con mioclonías de difícil manejo que solo presentó mejoría tras la suspensión definitiva del agonista adrenérgico β2. Se describen los hallazgos clínicos, las intervenciones y el resultado en las mioclonías asociadas con el uso de salbutamol y se discuten la posible génesis y la importancia de este efecto adverso. Para documentar el caso, se siguieron las recomendaciones de las guías para el reporte de casos (CAse REport, CARE). Aunque en diversos estudios se han descrito mioclonías secundarias al uso de diferentes fármacos, hasta donde se sabe, este sería el cuarto reporte de un caso asociado específicamente con el uso del salbutamol.

Abstract Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

Impact of economic sanctions on access to noncommunicable diseases medicines in the Islamic Republic of Iran

Background: It has been argued that economic sanctions and the economic crisis have adversely affected access to drugs. Aim: To assess the impact of economic sanctions on the Iranian banking system in 2011 and Central Bank in 2012 on access to and use of drugs for noncommunicable diseases [NCDs]. Methods: An interrupted time series study assessed the effects of sanctions on drugs for diabetes [5 drug groups], asthma [5 drug groups], cancer [14 drugs] and multiple sclerosis [2 drugs]. We extracted data from national reference databases on the list of drugs on the Iranian pharmaceutical market before 2011 for each selected NCD and their monthly sales. For cancer drugs, we used stratified random sampling by volume and value of sales, and source of supply [domestic or imported]. Data were analysed monthly from 2008 to 2013. Results: Market availability of 13 of 26 drugs was significantly reduced. Ten other drugs showed nonsignificant reductions in their market availability. Interferon alpha2b usage reduced from 0.014 defined daily doses per 1000 inhabitants per day [DID] in 2010 to 0.008 in 2013; and cytarabine from 1.40 mg per 1000 population per day in 2010 to 0.96 in 2013. Selective beta2-adrenoreceptor agonists usage reduced from 8.4 to 6.8 DID in the same time period. Conclusion: There is strong evidence that sanctions have had a negative effect on access to drugs, particularly those that depended on the import of their raw material or finished products

Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis / Antagonistas muscarínicos de longa duração vs. β 2 -agonistas de longa duração em exacerbações da DPOC: revisão sistemática e meta-análise

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

RESUMO Objetivo: Determinar se long-acting muscarinic antagonists (LAMAs, antagonistas muscarínicos de longa duração) são superiores a long-acting β2 agonists (LABAs, β2-agonistas de longa duração) na prevenção de exacerbações da DPOC. Métodos: Revisão sistemática e meta-análise de ensaios clínicos controlados aleatórios com pacientes com DPOC estável, de moderada a grave, conforme os critérios da Global Initiative for Chronic Obstructive Lung Disease, tratados com LAMA (brometo de tiotrópio, aclidínio ou glicopirrônio), acompanhados durante pelo menos 12 semanas e comparados a controles que usaram LABA isoladamente ou com um corticosteroide. Resultados: Foram analisados 2.622 estudos para possível inclusão com base em seu título e resumo; 9 estudos (17.120 participantes) foram incluídos na análise. Em comparação com LABAs, LAMAs resultaram em maior diminuição da razão da taxa de exacerbações [risco relativo (RR) = 0,88; IC95%: 0,84-0,93]; menor proporção de pacientes que apresentaram pelo menos uma exacerbação (RR = 0,90; IC95%: 0,87-0,94; p < 0,00001); menor risco de hospitalizações em virtude de exacerbação da doença (RR = 0,78; IC95%: 0,69-0,87; p < 0,0001) e menor número de eventos adversos sérios (RR = 0,81; IC95%: 0,67-0,96; p = 0,0002). A qualidade geral das evidências foi moderada para todos os desfechos. Conclusões: O principal achado desta revisão sistemática e meta-análise foi que LAMAs reduziram significativamente a taxa de exacerbações (episódios de exacerbação/ano), os episódios de exacerbação, as hospitalizações e os eventos adversos sérios.

Effect of salbutamol on the cardiovascular response in healthy subjects at rest, during physical exercise, and in recovery phase: a randomized, double-blind, crossover study

Aim: To evaluate the effect of the short-acting beta agonists (SABAs) salbutamol on cardiovascular response rest, exercise and recovery phase. Methods: This study was conducted as a randomized, double-blind, placebo controlled, crossover study in 15 healthy adults, with a mean age of 30.2±6.6 years. Participants underwent a maximal effort test on two non-consecutive days with 400 mcg of salbutamol or placebo. Throughout the protocol, the variables HR, blood pressure (BP), perceived rate of effort (modified Borg scale) and peak expiratory flow (PEF) were monitored. After salbutamol, baseline HR and PEF had increase from 71±8 to 80±11 bpm (p<0.05) and 454.0±64.5 to 475.3±71.4 L/min (p < 0.05), respectively. The variables HR, BP and Borg were similar between interventions during all the protocol phases (p>0.05). Conclusion: Administration of salbutamol increased rest heart rate; however, did not change heart rate, blood pressure and perceived exertion during exercise or recovery. This suggests that the salbutamol administration is safe and does not affect exercise intensity prescription in healthy subjects.(AU)

Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans / Impacto do tratamento de longo prazo com corticosteroides e broncodilatadores inalatórios na função pulmonar em um paciente com bronquiolite obliterante pós-infecciosa

ABSTRACT Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting 2 agonist combination, together with an inhaled long-acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance.

RESUMO A bronquiolite obliterante pós-infecciosa (BOPI) é uma doença das pequenas vias aéreas caracterizada por limitação fixa do fluxo aéreo. Portanto, os broncodilatadores e os corticosteroides inalatórios não são recomendados como opções de terapia de manutenção. Atualmente, o manejo da BOPI consiste apenas de um acompanhamento rigoroso dos pacientes afetados, visando à prevenção e ao tratamento precoce de infecções pulmonares. A incidência de BOPI tem aumentado na população pediátrica nos últimos anos. Os pacientes com BOPI caracterizam-se por um declínio progressivo da função pulmonar, associado a uma diminuição da capacidade funcional global. Relatamos aqui o caso de um homem relativamente jovem diagnosticado com BOPI, acompanhado por três anos. Após terapia de curto e de longo prazo com uma combinação de corticosteroide/2-agonista de longa duração inalatórios, associada a um agente antimuscarínico de longa duração inalatório, o paciente apresentou uma melhora relevante da obstrução das vias aéreas, a qual fora irreversível durante o teste de broncodilatação. A função pulmonar do paciente piorou quando ele interrompeu a terapia inalatória tripla. Além disso, um programa de reabilitação pulmonar de três semanas significativamente melhorou seu desempenho físico.

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility / Avaliação da resposta ao broncodilatador em pacientes pediátricos com bronquiolite obliterante pós-infecciosa: uso de diferentes critérios de identificação de reversibilidade das vias aéreas

ABSTRACT Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

RESUMO Objetivo: A bronquiolite obliterante pós-infecciosa (BOPI) é uma entidade clínica que tem sido classificada como obstrução fixa e constritiva do lúmen por tecido fibrótico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediátricos com BOPI, comparando critérios diferentes para a definição da resposta. Métodos: Foram avaliados pacientes pediátricos com diagnóstico de BOPI tratados em um de dois ambulatórios de pneumologia pediátrica na cidade de Porto Alegre (RS). Parâmetros espirométricos foram medidos de acordo com recomendações internacionais. Resultados: Foram incluídos 72 pacientes pediátricos com BOPI no estudo. As médias dos valores pré- e pós-broncodilatador foram claramente inferiores aos valores de referência para todos os parâmetros, especialmente FEF25-75%. Houve uma melhora pós-broncodilatador. Quando medidos como aumentos percentuais médios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as médias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressão viral, história familiar de asma e alergia não tiveram efeitos significativos na resposta ao broncodilatador. Conclusões: Pacientes pediátricos com BOPI têm uma obstrução das vias aéreas periféricas que responde ao tratamento, mas não uma reversão completa com o broncodilatador. O conceito de BOPI como obstrução fixa e irreversível parece não se aplicar a essa população. Nossos dados sugerem que a obstrução de vias aéreas em pacientes com BOPI é variável, e esse achado pode ter importantes implicações clínicas.

Avaliação dos efeitos vasculares e expressão de mRNA de receptores de drogas vasoconstritoras em leito arterial mesentérico de ratos normotensos, diabéticos, hipertensos renais um-rim, um clip (1R-1C) e 1R-1C diabéticos / Vascular reactivity and vasoconstrictor drugs receptors RNAmexpression on mesenteric artery bed of normotensive, diabetic, 1K-1C hypertensive and 1K-1C hypertensive-diabetic rats

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.(AU)

The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.(AU)

Research advances in gene polymorphisms in biological pathways of drugs for asthma / 中国当代儿科杂志

The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

Patrones de prescripción de broncodilatadores y corticoides inhalados en pacientes adultos de Colombia / Prescription patterns of bronchodilators and inhaled corticosteroids in adults of Colombia

Introducción: las enfermedades pulmonares obstructivas son frecuentes en pacientes mayores de 40 años y son causa de alta morbimortalidad a nivel mundial. En el presente estudio se describen los patrones de prescripción de medicamentos para su tratamiento en pacientes de Colombia. Material y métodos: estudio descriptivo observacional con pacientes, mayores de 40 años de ambos sexos, afiliados al Sistema General de Seguridad Social en Salud, en tratamiento continuo con broncodilatadores y/o corticoides inhalados entre septiembre y diciembre del año 2013, seleccionados a partir de una base de datos de dispensación de 6.5 millones de personas. Se recolectaron variables sociodemográficas, farmacológicas (fármacos con sus dosis diarias definidas), medicamentos concomitantes y clínicas (comorbilidades). Análisis mediante SPSS 22. Resultados: se incluyeron 6856 pacientes con una edad promedio de 73.8 ± 11.3 años, 54%fueron mujeres. Del total de pacientes 17.2% recibían monoterapia y 82.8% terapia combinada. El 74.3% de sujetos recibía β2-adrenérgicos, la mayoría (81.5%) de corta duración (BDCA), mientras que 33.3% de larga acción (BDLA). El 73.1% recibía anticolinérgicos distribuidos entre ipratropio (87.1%) y tiotropio (16.9%) y 71.7% recibía corticoides inhalados. Los medicamentos prescritos concomitantemente con mayor frecuencia fueron antihipertensivos (68.9%), antiulcerosos (56.1%) e hipolipemiantes (46.2%). Tener entre 40 y 55 o más de 80 años, recibir alguna medicación concomitante, utilizar corticoides inhalados, emplear monoterapia broncodilatadora y ser tratado en Bogotá y Cali, se asociaron de manera estadísticamente significativa con menor riesgo de recibir BDLA. Conclusiones: predomina la prescripción de BDCA, pese al limitado beneficio clínico reportado. La mayoría de broncodilatadores se emplean a dosis superiores a las recomendadas. Se considera necesario establecer estrategias educativas que mejoren los hábitos de prescripción. (Acta Med Colomb 2015; 40: 218-226).

Introduction: obstructive lung diseases are common in patients older than 40 years and cause high morbidity and mortality worldwide. The patterns of drugs prescription for its treatment in Colombian patients are described in this study. Methods: descriptive observational study with patients over 40 years of both sexes, members of the General System of Social Security in Health, in continuous treatment with bronchodilators and / or inhaled steroids between September and December 2013, selected from a dispensing database of 6.5 million people. Sociodemographic and pharmacological variables (drugs with defined daily doses), concomitant medications and co-morbidities were collected. Analysis using SPSS 22. Results: A total of 6856 patients were included with a mean age of 73.8±11.3 years, 54% were women. Of the total of patients, 17.2% received monotherapy and 82.8% combined therapy. 74.3% of subjects received β2-adrenergics, most (81.5%) short-acting bronchodilators, while33.3% long acting bronchodilators. 73.1% received anticholinergics distributed between ipratropium (87.1%) and tiotropium (16.9%) and 71.7% received inhaled steroids. The medications that were most often concomitantly prescribed, were antihypertensive (68.9%), antiulcerants (56.1%) and lipid lowering drugs (46.2%). To be between 40 and 55 or over 80 years, receive any concomitant medication, inhaled corticosteroid use, bronchodilator monotherapy use and being treated in Bogota and Cali, was statistically significantly associated with lower risk of receiving long-acting bronchodilators. Conclusions: the prescription of short-acting bronchodilators predominate despite the limited clinical benefit reported. Most bronchodilators are used at higher than recommended doses. It is necessary to establish educational strategies to improve prescribing habits. (Acta Med Colomb 2015; 40: 218-226).

Three-month Treatment Response and Exacerbation in Chronic Obstructive Pulmonary Disease

The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.

Stepping down in asthma.

Beta-2-agonists continue to find a dominant role in all the current guidelines on the management of chronic persistent bronchial asthma. However, the safety of the drugs remains doubtful. Thus, there is a case for review of the “Step up-Step down” approach in the management of chronic persistent bronchial asthma. Based on the currently available experimental and clinical data on bronchial asthma, the authors are of the opinion that chronic persistent bronchial asthma is best managed by a modified “Step I-Step II” approach.

golden factor in adherence to inhaled corticosteroid in asthma patients

Adherence to therapy is very important and many factors could be responsible for this issue. Suboptimal adherence to asthma therapy is a major contributor to poor asthma outcomes. Our aim is to find out the most important factor responsible for adherence to therapy in bronchial asthma patients. The study included 143 patients with persistent bronchial asthma. Factors that may affect adherence to therapy were studied. These factors included age, sex, residence, level of education, proper asthma education and whether inhaled corticosteroid [ICS] was taken alone, with long acting p2 agonist [LABA] in separate devices or with LABA in a combined form. Adherence to ICS was determined according to Medication Rating Scale. We found that 55.3% of patients that received asthma education were adherent to ICS while only 21% of patients that did not receive asthma education were adherent to ICS therapy. The difference was statistically highly significant [p = 0.003]. Other factors do not significantly affect adherence to ICS. Patients that used combined ICS with LABA in the same device were significantly more adherent to therapy [60.25%] than patients that used the same combination in 2 separate devices [34.5%]. All patients with well controlled asthma were adherent to ICS, while 47.5% of uncontrolled patients was adherent. Comparison between level of control and adherence to ICS was highly significant [p = 0.003]. This study showed how different factors may modulate adherence to asthma treatment and confirmed the importance of patient education in increasing adherence to asthma therapy

Efficacy and safety of tulobuterol patch versus oral salbutamol sulfate in children with mild or moderate acute attack of bronchial asthma: a comparative study / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To compare tulobuterol patch and oral salbutamol sulfate in terms of efficacy and safety in children with mild or moderate acute attack of bronchial asthma.</p><p><b>METHODS</b>A total of 92 children with mild and moderate acute asthmatic attack were randomly divided into salbutamol group (n=46) and tulobuterol group (n=46). Both groups received routine treatment with antihistamine, selective leukotriene receptor antagonist and glucocorticoid. In addition, the salbutamol group was given slow-release capsules of salbutamol sulfate, and the tulobuterol group was treated with tulobuterol patch. The two groups were compared with respect to symptom scores of cough, wheeze, respiratory rate, wheezing sound, three depression sign and peak expiratory flow, as well as adverse events.</p><p><b>RESULTS</b>As the treatment proceeded, symptom scores decreased in both groups; on the third day of treatment, all symptom scores except cough score showed a significant decrease in both groups (P<0.05), but the tulobuterol group had significantly lower symptom scores than the salbutamol group (P<0.05). On the fourteenth day of treatment, both groups had a significant decrease in cough score (P<0.05), but the tulobuterol group had a significantly lower cough score than the salbutamol group (P<0.05). One child developed hand trembling in the salbutamol group, while no adverse event occurred in the tulobuterol group.</p><p><b>CONCLUSIONS</b>Compared with oral salbutamol sulfate, tulobuterol patch has a better therapeutic efficacy and a higher safety in children with mild or moderate acute asthmatic attack.</p>

Rapid determination of illicit beta2-agonist additives in health foods and traditional Chinese patent medicines with DCBI-MS/MS method / 药学学报

A novel rapid method for detection of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines was developed with the desorption corona beam ionization mass spectrometry (DCBI-MS) technique. The DCBI conditions including temperature and sample volume were optimized according to the resulting mass spectra intensity. Matrix effect on 9 beta2-agonists additives was not significant in the proposed rapid determination procedure. All of the 9 target molecules were detected within 1 min. Quantification was achieved based on the typical fragment ion in MS2 spectra of each analyte. The method showed good linear coefficients in the range of 1-100 mg x L(-1) for all analytes. The relative deviation values were between 14.29% and 25.13%. Ten claimed antitussive and antiasthmatic health foods and traditional Chinese patent medicines from local pharmacies were analyzed. All of them were negative with the proposed DCBI-MS method. Without tedious sample pretreatments, the developed DCBI-MS is simple, rapid and sensitive for rapid qualification and semi-quantification of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines.