Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases / Posicionamento da Academia Brasileira de Rinologia sobre o uso de anti-histamínicos, antileucotrienos e corticosteroides orais no tratamento de doenças inflamatórias nasossinusais

Abstract Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors’ needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugs; however, final considerations about the role of each of them have been made.

Resumo Introdução: As afecções inflamatórias do nariz e dos seios paranasais são muito prevalentes na população geral, causam acentuada perda de qualidade de vida dos pacientes afetados, geram perdas significativas das atividades de trabalho, lazer e sociais. Esses pacientes necessitam de tratamento específico e especializado e uma ampla gama de medicações orais está disponível. Objetivo: O presente documento tem por objetivo esclarecer àqueles que tratam das doenças nasossinusais inflamatórias, tanto especialistas quanto generalistas, sobre as terapêuticas orais nas afecções inflamatórias nasais não infecciosas. Método: A metodologia usada para elaboração deste artigo incluiu a busca das palavras chave: corticosteroides orais, anti-histamínicos, antileucotrienos, rinite, rinossinusite nos bancos de dados Medline e Embase nos últimos 5 anos. Como não foi achado artigo relevante para o texto sobre o assunto de interesse nos últimos 5 anos, a busca foi estendida por mais 5 anos, e assim por diante, de acordo com a necessidade dos autores. Resultados: Literatura relevante foi encontrada com relação ao uso dos anti-histamínicos, antileucotrienos e corticosteroides orais nessas afecções. A Academia Brasileira de Rinologia ressalta, após amplo debate do colegiado, pontos-chave no tratamento com esses medicamentos. Conclusão: Há respaldo na literatura para o uso desses medicamentos, entretanto considerações finais acerca do papel de cada deles foram feitas.

The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals / Efecto de montelukast en un modelo de artritis gotosa inducido por cristales de monourato de sodio

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

Efficacy of montelukast and loratadine as treatment for allergic rhinitis in children.

The objective of this study was to compare the effectiveness of montelukast combined with loratadine once daily to loratadine alone for a 2-week treatment course of allergic rhinitis in a randomized, double-blind placebo controlled trial which enrolled 115 children, 6- 15-years-old. The patients were randomly assigned to receive montelukast and loratadine (treatment group) or placebo and loratadine (control group). The primary outcome was the mean percent change of the total daytime nasal symptom scores (PDTS) and secondary outcomes were the mean percent changes of the nighttime nasal, daytime eye and composite symptom scores (PNTS, PES, PCS), as well as the nasal secretion, turbinate swelling and nasal congestion scores (PNSS, PTSS, PNCS). There were no significant differences in the PDTS of the 2 groups. The change in the night time nasal congestion score (PNTS-congestion) was higher in the treatment group, but not statistically significant (p = 0.077). Only the mean percent change in decreased turbinate swelling was significantly greater in the montelukast and loratadine group than the loratadine alone group (-22 +/- 7 vs. -1 +/- 5, p < 0.05).

Uso de zafirlucaste para o tratamento de contraturacapsular: estudo preliminar / Zafirlukaste use for capsular contracture treatment: preliminary report

Introdução: A contratura capsular é definida como uma cicatrização esférica com contração da cápsula que envolve a prótese. Medicações usadas para o tratamento de asma brônquica foram relatadas em estudos anteriores como eficazes no tratamento de contratura capsular. Este estudo avaliou o uso de zafirlucaste para tratamento de contratura capsular. Método: Foram avaliadas oito pacientes (12 mamas) que desenvolveram contratura capsular após mamoplastia de aumento, mastopexia com uso de prótese e troca de prótese mamária. Depois de detectada contratura, foi instituído o uso de zafirlucaste 20 mg, via oral, de 12/12 horas, por um período que variou de 30 a 90 dias. Resultados: Houve resolução completa da contratura, com retorno a Baker grau I em seis pacientes (nove mamas). Houve redução dograu de contratura Baker III para Baker II em uma paciente (duas mamas). Não houve respostaao uso da medicação em uma paciente (uma mama), que manteve Baker grau III mesmo após90 dias de uso de zafirlucaste. A redução do grau de contratura com o uso de zafirlucaste foi estatisticamente significante (p= 0,001). Clinicamente nenhuma paciente apresentou efeitos colaterais ao uso da medicação. Conclusão: Os resultados desta análise clínica sugerem uma resposta favorável ao uso de zafirlucaste para o tratamento de contratura capsular.

Introduction: Capsular contracture is defined as a spherical scar with contraction of the capsule involving the prosthesis. Medications used for the treatment of bronchic asthma have being cited in previous studies as being efficient in capsular contracture treatment. This study assessed the use of zafirlukaste for the treatment of capsular contracture. Methods: Eight patients (12 breasts)were evaluated, who developed capsular contracture after augmentation mammoplasty, mastopexy and mammary prosthesis exchange. After the diagnosis of the contracture, it was begun the use of zafirlukaste 20mg oral intake twice daily for a period varying between 30 and 90 days. Results: There was complete resolution of the contracture, returning to Baker grade I in six patients (nine breasts). There was reduction on Baker grade from III to II in one patient (two breasts). There was no response to medication use in one patient (one breast) that maintained Baker grade III even after 90 days using zafirlukaste. The reduction of the grade of contracture with the use of zafirlukaste was statistically significant (p=0.001). Clinically, none patient presented the medication’s side effects. Conclusion: The results of this clinical assessment suggest a favorable response of the use of zafirlukaste for the treatment of capsular contracture.

Anti-leukotrienes in asthma: yet to arrive.

Inflammation plays a predominant role in the pathogenesis of asthma. The leukotrienes (LTs) exert their actions by binding to and activating various receptors. Leukotrienes B4, C4, D4, and E4 have been shown experimentally to play a role in inflammatory mechanisms, producing the pathologic changes seen in asthma. Antileukotrienes represent a new class of anti-asthma drugs with anti-inflammatory role. In asthma management, LT modifiers from the groups of 5 lipoxygenase inhibitor and Cys LT1 receptor antagonists are found useful. LAs are of main use in mild to moderate chronic asthma. Their usefulness is also observed in allergic rhinitis and even in severe chronic cases of asthma which are resistant to steroids. In chronic asthma they are required to be used for prolonged periods with other agents viz. inhaled steroids and beta 2 agonists. These agents are essentially safe. Except for Montelukast, which can be used in children above six years of age, the paediatric use of other agents is yet to be established. LAs are gradually becoming available in increasing number of countries. In India, we have to presumably wait for sometime before these drugs reach the market. The cost of LAs is reasonably high. Thus, India awaits arrival of LAs, may be for good, as more concrete information from various trials will permit us to practice more evidence based medicine.