Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Eficácia e segurança de tripla terapia broncodilatadora comparada à dupla terapia em DPOC grave: revisão rápida de evidências / Effectiveness and safety of triple bronchodilator therapy compared to dual therapy in severe COPD: rapid response review of evidence

Tecnologia: Tripla terapia broncodilatadora (vilanterol/ umeclidínio/ fluticasona, formoterol/ glicopirrônio/ beclometasona) e dupla terapia. Indicação: Tratamento de doença pulmonar obstrutiva crônica (DPOC), formas grave e muito grave. Pergunta: Há diferenças de efeito nos principais desfechos de eficácia e segurança entre a tripla terapia broncodilatadora e as duplas terapias no tratamento de pacientes com DPOC, formas grave e muito grave? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluídas 2 revisões sistemáticas. Conclusão: A tripla terapia broncodilatadora era mais eficaz que a dupla terapia para reduzir a taxa anual de exacerbações moderadas a severas, mas não tinha superioridade para obter ganhos clínicos em outros desfechos (volume expiratório forçado no primeiro segundo, qualidade de vida, índice de dispneia, mortalidade geral, mortalidade respiratória), exceto que a tripla terapia era superior à dupla terapia com agonistas beta-2/ antagonistas antimuscarínicos e similar à dupla terapia com agonistas beta-2/ corticoesteróides inalatórios para reduzir mortalidade. A tripla terapia tinha perfil de segurança similar à dupla terapia, com mesmo risco para eventos adversos e eventos adversos graves. A tripla terapia tinha maior risco para pneumonias que a dupla terapia com agonistas beta-2/ antagonistas antimuscarínicos

Technology: Triple bronchodilator therapy (vilanterol/ umeclidinium/ fluticasone, formoterol/ glycopyrronium/ beclomethasone) and dual therapy. Indication: Treatment of chronic obstructive pulmonary disease (COPD), severe and very severe forms. Question: Are there differences in effects of efficacy and safety outcomes between triple bronchodilator therapy and dual therapies in treating patients with severe and very severe forms of COPD? Methods: Rapid review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: Two systematic reviews were selected and included. Conclusion: Triple bronchodilator therapy was more effective than dual therapy in reducing the annual rate of moderate to severe exacerbations, but had no superiority for clinical gains in other outcomes (forced expiratory volume in first second, quality of life, dyspnea index, general mortality, respiratory mortality), except that, for reducing mortality, triple therapy was superior to dual therapy with beta-2 agonists/ antimuscarinic antimuscarinics and similar to dual therapy with beta 2 agonists/ inhaled corticosteroids. The triple therapy had a similar safety profile to dual therapy, with the same risk for adverse events and serious adverse events. The triple therapy had a higher risk for pneumonia than a dual therapy with beta-2 agonists/ antimuscarinic antagonists

Impacto da fluticasona intranasal em pacientes com apneia obstrutiva do sono: um estudo prospectivo / The impact of intranasal fluticasone on patients with obstructive sleep apnea: a prospective study

Resumo Introdução: A apneia obstrutiva do sono é o tipo mais comum de apneia do sono, causada por obstrução completa ou parcial da via aérea superior. A obstrução nasal também é considerada como um dos fatores de risco independentes da apneia obstrutiva do sono. Objetivo: Avaliar pacientes com apneia obstrutiva do sono. Método: Pacientes com apneia obstrutiva do sono foram incluídos no estudo de junho a dezembro de 2015, tratados com spray de corticosteroide intranasal por quatro semanas. Vários parâmetros foram obtidos antes e após o tratamento, inclusive os escores da escala Nasal Obstruction Symptom Evaluation, do Pittsburgh Sleep Quality Index e do questionário Escala de Sonolência de Epworth. Resultados: Cinquenta pacientes completaram os questionários antes e após o tratamento intranasal com fluticasona. A média de idade era de 39,7 ± 15,6 anos, com uma proporção de homens para mulheres de 3:2. Os escores pós-tratamento da Escala de Sonolência de Epworth, do Pittsburgh Sleep Quality Index e do Nasal Obstruction Symptom Evaluation indicaram uma diminuição em comparação aos escores pré-tratamento, de 10,4 para 8,74, 7,86 para 6,66 e 9,08 para 6,48, respectivamente. Uma diminuição significativa foi observada no grupo Nasal Obstruction Symptom Evaluation ≥ 10 em todas as três categorias, mas não no grupo Nasal Obstruction Symptom Evaluation <10. Conclusões: Os autores concluíram que o tratamento com fluticasona intranasal pode ser útil em pacientes com apneia obstrutiva do sono relacionada a obstrução nasal para melhorar a qualidade do sono e limitar a disfunção diurna.

Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.@*METHODS@#A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.@*RESULTS@#Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.@*CONCLUSIONS@#SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.@*PROSPERO REGISTRATION NUMBER@#CRD42019133156.

Hemosiderosis pulmonar idiopática (HPI): presentación de un caso y revisión de la literatura / Idiopathic pulmonary hemosiderosis (IPH): a case report and review of the literature

We present the case-report of a one-month-old infant, admitted to the Emergency Department with hypovolemic shock secondary to pulmonary hemorrhage who required life-support measures, including vasoactive drugs and methylprednisolone pulses. She was discharged from the hospital after 13 days of evolution and then readmitted 5 days later for a new episode of hemoptysis with hemodynamic compromise. Fiberoptic bronchoscopy was performed 4 days after the first episode showed a normal anatomy, without active bleeding, with 20% of hemosiderophages in bronchoalveolar lavage. Diffuse infiltrates were found on the chest radiograph. Differents studies were performed for check-out infection, heart disease, immune disease, thrombophilia, celiac disease, swallowing disorder, vascular abnormalities and allergy to cow's milk protein were negative, which led to Idiopathic Pulmonary Hemosiderosis (IPH). It was managed with amino acid formula, daily oral prednisone until 6 months of age and then every other day, and permanent inhaled fluticasone. In subsequent controls, normal growth and development were found, with no recurrences up to the time of this report, at 1 year of age. The favorable evolution in this case is attributed to early diagnosis and timely treatment with systemic corticosteroids. A review of the topic of IPH in pediatrics is presented, and study and treatment algorithms are proposed.

Se presenta el caso de una lactante de un mes de edad, que se presentó en el Servicio de Urgencia con shock hipovolémico secundario a hemorragia pulmonar. Necesitó medidas de soporte vital, incluyendo drogas vasoactivas y pulsos de metilprednisolona. Egresó del hospital a los 13 días de evolución y reingresó 5 días después por nuevo episodio de hemoptisis con compromiso hemodinámico. La fibrobroncoscopía efectuada a los 4 días de evolución del primer episodio mostró una anatomía normal, sin sangrado activo, con 20% de hemosiderófagos en el lavado broncoalveolar. En la radiografía de tórax se encontró infiltrados difusos. Los estudios en busca de infección, cardiopatía, enfermedad inmunológica, trombofilia, enfermedad celíaca, trastorno de deglución, anomalías vasculares y alergia a la proteína de la leche de vaca resultaron negativos, por lo que se planteó una Hemosiderosis Pulmonar Idiopática (HPI). Se manejó con fórmula aminoacídica, prednisona oral diaria hasta los 6 meses de edad y después en días alternos y fluticasona inhalada permanente. En controles posteriores se constató crecimiento y desarrollo normal, sin recidivas hasta el momento de este reporte, con 1 año de edad. La evolución favorable en este caso se atribuye al diagnóstico precoz y tratamiento oportuno con corticoides sistémicos. Se presenta una revisión del tema de HPI en pediatría y se proponen algoritmos de estudio y tratamiento.

Síndrome de Cushing exógeno por interacción medicamentosa de ritonavir y fluticasona inhalada. Reporte de tres casos pediátricos / Exogenous Cushing syndrome due to drug interaction of ritonavir and inhaled fluticasone. Report of three pediatric cases

El incremento de la expectativa de vida con el advenimiento de la terapia antirretroviral de alta eficacia plantea desafíos en cuanto a la toxicidad e interacciones medicamentosas. El síndrome de Cushing exógeno por interacción entre ritonavir y fluticasona inhalada en niños con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica es infrecuente. Hasta el momento, hay 20 casos reportados. Se describen 3 casos pediátricos con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica que presentaron síndrome de Cushing exógeno con fluticasona inhalada en dosis habituales por la interacción medicamentosa entre esta y ritonavir. Los pacientes resolvieron el cuadro clínico luego de 2-4 meses de suspensión de la fluticasona y permanecieron asintomáticos en el seguimiento

The increase in life expectancy with the advent of highly effective antiretroviral therapy poses challenges in terms of toxicity and drug interactions. Exogenous Cushing syndrome by interaction between ritonavir and inhaled fluticasone in children diagnosed with human immunodeficiency virus infection and chronic pulmonary pathology is rare. So far, there are 20 cases reported. Three pediatric cases are reported, with a diagnosis of human immunodeficiency virus infection and chronic pulmonary pathology who presented exogenous Cushing syndrome with inhaled fluticasone at usual doses due to drug interaction between it and ritonavir. The patients resolved the clinical Síndrome de Cushing exógeno por interacción medicamentosa de ritonavir y fluticasona inhalada. Reporte de tres casos pediátricos Exogenous Cushing syndrome due to drug interaction of ritonavir and inhaled fluticasone. Report of three pediatric cases picture after 2-4 months of fluticasone suspension and remain asymptomatic in the follow-up.

Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Treatment adherence and level of control in moderate persistent asthma in children and adolescents treated with fluticasone and salmeterol / Adesão ao tratamento e nível de controle da asma persistente moderada em crianças e adolescentes tratados com fluticasona e salmeterol

Abstract Objective: There is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination-metered aerosol and the level of asthma control in children. Methods: This was a prospective observational study of 84 patients aged 5-16 years with moderate persistent asthma, who remained uncontrolled despite the use of 1000 µg/day of inhaled nonextrafine-hydrofluoric alkane-beclomethasone dipropionate in the three months prior to study enrollment. Participants were prescribed two daily doses of FP (125 µg)/salmeterol xinafoate (25 µg) combination by metered aerosol/spacer for six months. Adherence rates were assessed using the device's dose counter after the 2nd, 4th, and 6th months of follow up. Asthma control was assessed using a simplified Global Initiative for Asthma 2014 Report classification. Results: Mean adherence rates after the second, fourth, and sixth months were 87.8%, 74.9%, and 62.1% respectively, for controlled asthma, and 71.7%, 56.0%, and 47.6% respectively, for uncontrolled asthma (all p-values ≤ 0.03). The proportion of children achieving asthma control increased to 42.9%, 67.9% and 89.3% after the 2nd, 4th and 6th months of follow-up, respectively (p ≤ 0.001). Conclusion: Adherence rates between 87.8% in the 2nd month and 62.1% in the 6th month were strong determinants of asthma control.

Resumo Objetivo: São escassos os estudos que avaliaram a relação entre a taxa de adesão à combinação de proprionato de fluticasona/xinafoato de salmeterol e o nível de controle da asma na infância. O presente estudo teve como objetivo avaliar essa relação. Métodos: Estudo prospectivo observacional com 84 participantes, de 5 a 16 anos, todos eles com asma persistente moderada que permaneceram não controlados apesar do uso de 1.000 µg/dia de dipropionato de beclometasona em partículas não extrafinas nos três meses que antecederam a admissão no estudo. Os participantes receberam prescrição de 125 µg de propionato de fluticasona e 25 µg xinafoato de salmeterol através de inalador pressurizado, duas vezes ao dia, e foram avaliados após o 2°, 4° e 6° meses de tratamento. A taxa de adesão foi obtida por meio do contador analógico de doses incorporado ao inalador. A classificação do nível de controle da asma foi baseada numa simplificação das recomendações da Global Initiative for Asthma. Resultados: As taxas de adesão aos 2, 4 e 6 meses para a asma controlada foram 87,8%, 74,9% e 62,1% e para a asma não controlada de 71,7%, 56,0% e 47,6% (p ≤ 0,03), respectivamente. A proporção de pacientes com asma controlada elevou- se para 42,9%, 67,9% e 89,3% nas três avaliações subsequentes (p ≤ 0,001). Conclusões: Taxas de adesão entre 87,8% no 2° mês e de 62,1% no 6° mês foram determinantes para o nível de controle da asma.

Clinical effect of fluticasone propionate, montelukast sodium and ketotifen in treatment of cough variant asthma in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA).@*METHODS@#A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence.@*RESULTS@#After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P0.0024).@*CONCLUSIONS@#For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.

The Effects of Olfactory Training with Intranasal Corticosteroid Spray in Korean Patients with Olfactory Dysfunction

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.

Evaluación clínica del tratamiento de la rinitis alérgica perenne con spray nasal de Fluticasona y Azelastina / Clinical evaluation of perennial allergic rhinitis treatment with Fluticasone and Azelastine nasal spray

Introducción: La azelastina es un antihistamínico tópico nasal, exento de los molestos efectos sistémicos, la cual asociada con fluticasona, ha mostrado excelentes resultados en el control de la rinitis alérgica. Objetivo: Evaluar los resultados del tratamiento del spray nasal de azelastina y fluticasona. Diseño: Observacional descriptivo prospectivo. Materiales y métodos: Se evaluaron 76 pacientes de ambos sexos, con edades entre los 12 y 59 años, con diagnóstico de rinitis alérgica en el que se midieron los síntomas: obstrucción, prurito, estornudos y rinorrea. La severidad de los síntomas fue valorada por el propio paciente de 0 a 10 pretratamiento, a la semana, dos, tres y cuatro semanas de iniciado el tratamiento, el cual fue igual para todos los pacientes, con control ambiental y la atomización de 2 puff en cada fosa nasal del spray de azelastina y fluticasona. Se hizo seguimiento de los síntomas nasales y la aparición de efectos colaterales. Resultados: Se observó una diferencia estadísticamente significativa entre el puntaje obtenido previo al tratamiento y en la evaluación posterior desde la primera semana de uso y hasta el momento del seguimiento final a la cuarta semana (p<0,0001 Friedman F). Conclusiones: El spray nasal de azelastina y fluticasona, es muy útil en el control de los síntomas de rinitis alérgica, mostrando además un adecuado perfil de seguridad.

Introduction: Azelastine, is a topical nasal antihistamine free of systemic effects, the quality associated with fluticasone, has been excellent in the control of allergic rhinitis. Objective: To evaluate the results of the treatment of the nasal spray of azelastine and fluticasone. Design: Prospective and descriptive study. Methods: 76 patients of both sexes, aged between 12 and 59 years, with a diagnosis of allergic rhinitis in which the symptoms were measured: obstruction, pruritus, sneezing and rhinorrhea. The severity of each symptom was assessed by the patient from 0 to 10 before and after a week, two, three and four weeks, which was the same for all patients, with environmental control and the atomization of 2 puffs in each nostril of the azelastine and fluticasone spray. A follow-up of nasal symptoms and the appearance of side effects. Results: A statistically significant difference was observed between the score obtained before the treatment and in the subsequent evaluation from the first week until the time of the final follow-up at the fourth week (p <0.0001 Friedman F). Conclusion: The nasal spray of azelastine and fluticasone is very useful in the control of the symptoms of allergic rhinitis.

Assessment of leukotriene E4 in exhaled breath condensate as a marker of inflammation and therapeutic effect in allergic rhinitis children

PURPOSE: Recent studies have shown that the cysteinyl leukotriene (cysLT) of exhaled breath condensate (EBC) could be predictive of inflammatory status and effectiveness of treatment in allergic disease. The aim of this study was to evaluate the inflammation and therapeutic effectiveness of cysLT in EBC in pediatric patients with allergic rhinitis (AR). METHODS: We enrolled 34 healthy children (median age, 4 years 10 months) and 67 AR children (median age, 5 years 1 month). All of the AR patients received intranasal steroid (fluticasone furoate) once daily for 2 weeks. After 2 week of fluticasone furoate treatment, they were classified into 2 groups: the fluticasone furoate (F) and montelukast (M) groups. We treated each group for another 8 weeks. To evaluate the therapeutic effectiveness, we used symptom score (SS) and EBC leukotriene E4 (LTE4). EBC samples were collected with RTube. Each parameter was checked at 0, 2, and 10 weeks of therapy. RESULTS: Most of the AR patients showed clinical improvement with 2- and 10-week fluticasone therapy (F group: 0-week SS, 5.6; 2-week SS, 3.6; 10-week SS, 2.1; P<0.01; M group: 0-week SS, 4.8; 2-week SS, 3.2; 10-week SS, 1.9: P<0.01). LTE4 levels were higher in AR patients than in control subjects (0 week: 87 pg/mL vs. 18 pg/mL) and were reduced after 2 weeks of fluticasone treatment (F group: 90→51.6 pg/mL, P<0.01; M group: 84→46.1 pg/mL, P<0.01). After 10 weeks of treatment, there was no significant difference in the LTE4 level between the F and M groups. CONCLUSION: LTE4 in EBC may be useful for evaluating inflammation and therapeutic effectiveness in patients with allergic rhinitis.

Pharmacokinetic characteristics of fluticasone, salmeterol and tiotropium after concurrent inhalation

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.

Síndrome de Cushing iatrogénico por corticoides inhalados en paciente VIH / Cushing syndrome in a HIV patient using inhaled steroids: report of one case

We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.

Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model

BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.

Efficacy of fluticasone propionate aerosol versus budesonide suspension in treatment of recurrent wheezing caused by bronchiolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of fluticasone propionate aerosol (flixotide) versus budesonide suspension in the treatment of recurrent wheezing caused by bronchiolitis.</p><p><b>METHODS</b>A total of 214 infants with newly diagnosed bronchiolitis were randomly divided into flixotide treatment (106 infants) and budesonide treatment groups (108 infants), and were given aerosol inhalation of flixotide or budesonide for 3 months after achieving remission of clinical symptoms. Another 136 infants with bronchiolitis who did not receive regular inhalation of corticosteroid after achieving remission of clinical symptoms were enrolled as the control group. The follow-up visits were performed for 1 year, and the effects of the two therapeutic methods on recurrent wheezing were evaluated.</p><p><b>RESULTS</b>Compared with the control group, both the flixotide and budesonide treatment groups had significantly fewer times of wheezing episodes within 1 year and a significantly lower recurrence rate of wheezing within the first 3 months after regular inhalation of corticosteroid, but no significant differences were observed between the two treatment groups. The amount of corticosteroid inhaled and hospital costs in the budesonide treatment group were significantly higher than in the flixotide treatment group (P<0.01).</p><p><b>CONCLUSIONS</b>Continuous inhalation of flixotide or budesonide after remission of clinical symptoms in children with bronchiolitis can reduce wheezing episodes and the recurrence of wheezing, and flixotide treatment is superior to budesonide treatment in the aspects of hospital costs and the amount of corticosteroid used.</p>

Propionato de fluticasona para o tratamento de crianças e adultos com asma moderada a grave / Fluticasone propionate for the treatment of children and adults with moderate to severe asthma

CONTEXTO: A asma é uma doença inflamatória crônica das vias aéreas associada à hiperresponsividade das vias aéreas, que leva a episódios recorrentes de sibilos, dispneia, opressão torácica e tosse, particularmente à noite ou no início da manhã. A asma brônquica é uma das doenças crônicas mais comuns, acometendo crianças e adultos, ao redor do mundo. Estima-se que existam 20 milhões de asmáticos no Brasil, considerando-se uma prevalência global de 10%. A base do tratamento medicamentoso da asma persistente, em consonância com o conhecimento atual da fisiopatologia, é o uso continuado de medicamentos com ação anti-inflamatória, também chamados controladores, sendo corticosteroides inalatórios os principais deles. No Brasil, está em vigor o Protocolo Clínico e Diretriz Terapêutica de asma por meio da Portaria SAS/MS nº 1.317 - 25/11/2013 (alterado pela Portaria SAS/MS nº 603, de 21 de julho de 2014), na qual são recomendados os seguintes fármacos: beclometasona, budesonida, fenoterol, formoterol, formoterol associado à budesonida, salbutamol, salmeterol, prednisona e prednisolona. O demandante apresentou dossiê técnico solicitando a incorporação do Flixotide® (propionato de fluticasona) à relação de fármacos disponíveis no SUS, como mais uma opção clínica no arsenal terapêutico de tratamento de asma no Brasil, alegando que, além de ser mais uma alternativa, essa incorporação geraria economia e competitividade no mercado de corticoides inalatórios. EVIDÊNCIAS CIENTÍFICAS: Analisou-se o conjunto de evidências encaminhado pelo demandante, no qual foram incluídas três revisões sistemáticas e 18 ensaios clínicos randomizados, sendo que nove deles compararam o propionato de fluticasona com a beclometasona e os outros nove com a budesonida. Os resultados dos estudos mostraram que não há diferença estatisticamente significante tanto para eficácia, medida pela função pulmonar, como para a segurança entre os medicamentos comparados. De acordo com os resultados dos estudos, a efetividade deste medicamento é similar àquela de outros corticoides inalatórios, não apresentando diferenças expressivas nos eventos adversos, quando utilizados em doses equipotentes. RECOMENDAÇÃO DA CONITEC: A CONITEC, em sua 37ª reunião ordinária realizada no dia 02/07/2015, deliberou por unanimidade recomendar a não incorporação da fluticasona para a redução dos sintomas e exacerbações da asma em pacientes tratados com broncodilatadores isolados ou outra terapia profilática. CONSULTA PÚBLICA: Foram recebidas 99 contribuições na consulta pública, sendo 88 de paciente/responsável e 11 de conteúdo técnico-científico. Em geral, as contribuições foram a favor da incorporação da fluticasona. Os principais motivos citados incluem mais uma opção para o tratamento de asma, menor dose necessária para obter os efeitos desejados e que a fluticasona tem um menor impacto no crescimento de crianças. A empresa fabricante da tecnologia fez uma contribuição com observações sobre o cálculo da estimativa de impacto orçamentário, essas observações foram analisadas e o impacto orçamentário foi revisado, chegando a uma estimativa que varia entre uma economia de aproximadamente R$ 16 milhões e gasto adicional de R$ 110 milhões no primeiro ano após incorporação, e entre uma economia de R$ 89 milhões e gasto adicional de R$ 583 milhões no total dos próximos 5 anos após a incorporação. DELIBERAÇÃO FINAL: Aos 03 (três) dias do mês de setembro de 2015, reuniu-se a Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ CONITEC, regulamentada pelo Decreto nº 7.646, de 21 de dezembro de 2011, que, na presença dos membros, deliberou por unanimidade recomendar a não incorporação da fluticasona para a redução dos sintomas e exacerbações da asma em pacientes tratados com broncodilatadores isolados ou outra terapia profilática. Foi assinado o Registro de Deliberação nº142/2015. DECISÃO: Não incorporar a fluticasona para a redução dos sintomas e exacerbações da asma em pacientes tratados com broncodilatadores isolados ou outra terapia profilática no âmbito do Sistema Único de Saúde - SUS. Portaria nº 46, de 29 de setembro de 2015.

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.