Effect mechanism of acupuncture for anti-asthmatic airway remodeling based on TGF-β1 / Smad3 signaling pathway / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6) + "Yuji" (LU 10) for the airway remodeling in asthma rats based on the transforming growth factor-β1 (TGF-β1)/ Smad family member 3 (Smad3) signaling pathway; and explore the efficacy difference between the two acupoint combinations.@*METHODS@#Forty SPF male SD rats, aged 4 weeks, were randomly divided into a blank group (n = 10) and a modeling group (n = 30). The ovalbumin (OVA) sensitization method was used to establish asthma model in the modeling group. After successful model preparation, the rats of the modeling group were randomized into a model group, an acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) (AAF) group, and acupuncture at "Kongzui" (LU 6)+"Yuji" (LU 10) (AAK) group, with 10 rats in each one. Starting from day 15 of the experiment, 5 min after motivating, acupuncture was applied to "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6)+"Yuji" (LU 10) in the AAF group and the AAK group respectively. The intervention was delivered for 30 min each time, once daily, lasting 3 weeks consecutively. Using lung function detector, the airway resistance (RL) and dynamic compliance (Cdyn) of the lungs were detected. The histomorphology of lung tissues was detected with HE staining and Masson staining, and the mRNA and protein expression of TGF-β1 and Smad3 in lung tissues was detected with the real-time PCR and Western blot methods.@*RESULTS@#Compared with the blank group, RL was increased and Cdyn was decreased in the rats of the model group (P<0.01); and RL was reduced and Cdyn was increased in the AAF group and the AAK group when compared with those in the model group (P<0.01, P<0.05). The rats of the model group had bronchial lumen stenosis, inflammatory cell infiltration, collagen fibre hyperplasia and thickened smooth muscle in the lung tissues when compared with those in the blank group; and in comparison with the model group, all of the above morphological changes were attenuated in the AAF group and the AAK group. Besides, these morphological changes of the lung tissues were more alleviated in the AAF group when compared with those in the AAK group. In comparison with the blank group, the mRNA and protein expression of TGF-β1 and Smad3 of the lung tissues was increased in the model group (P<0.01), and it was reduced in the AAF group and the AAK group when compared with that in the model group (P<0.05, P<0.01). The mRNA expression of TGF-β1 and Smad3 was lower in the AAF group when compared with that in the AAK group (P<0.05).@*CONCLUSION@#Acupuncture at either "Feishu" (BL 13)+"Dingchuan" (EX-B 1) or "Kongzui" (LU 6)+"Yuji" (LU 10) reduces the airway remodeling in the rats with asthma, which may be related to the down-regulation of mRNA and protein expression of TGF-β1 and Smad3. The better efficacy is obtained with acupuncture at "Feishu" (BL 13)+"Dingchuan" (EX-B 1).

Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year / 中华预防医学杂志

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

Reações adversas do montelucaste no tratamento da asma pediátrica: uma revisão integrativa da literatura / Adverse reactions of montelukast in the treatment of pediatric asthma: an integrative literature review / Reacciones adversas de montelukast en el tratamiento del asma pediátrico: una revisión integrativa de la literatura

Buscou-se analisar as reações adversas do montelucaste quando prescrito para o tratamento da asma pediátrica. Revisão integrativa da literatura utilizando as bases de dados: U.S. National Library of Medicine (PubMed), Biblioteca Virtual da Saúde (BVS), SCOPUS e Business Source Complete (EBSCO), empregando os descritores: "asthma", "pediatric", "montelukast" e "adverse effects", unidos pelo booleano "AND''. Incluíram-se artigos na íntegra; publicados nos últimos 5 anos; redigidos em português, inglês ou espanhol; pesquisados em humanos e com uma relação com o nosso objetivo. Excluíram-se os que se enquadravam em nossos critérios de exclusão.Foram identificados 53 artigos, dos quais 11 compuseram a amostra final desta revisão. A exposição ao montelucaste foi associada a uma chance 2 vezes maior de reações neuropsiquiátricas em um dos artigos analisados, porém os estudos ainda não forneceram uma explicação fisiopatológica em comum. Reações neuropsiquiátricas foram as de maior prevalência, representando mais de 90% da amostra.

We analyzed the adverse reactions of montelukast when prescribed for the treatment of pediatric asthma. This is an integrative literature review using the databases: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Business Source Complete (EBSCO), using the descriptors: "asthma", "pediatric", "montelukast" and "adverse effects", connected by the Boolean " AND''. Articles in full were included, published in the last 5 years, written in Portuguese, English or Spanish, researched in humans and related to our objective. Those that met our exclusion criteria were excluded. Fifty-three articles were identified, of which 11 comprised the final sample of this review. Exposure to montelukast was associated with a 2-fold greater chance of neuropsychiatric reactions in one of the articles analyzed, but the studies have not yet provided a common pathophysiological explanation. Neuropsychiatric reactions were the most prevalent, representing more than 90% of the sample.

Se intentó analizar las reacciones adversas de montelukast cuando se prescribe para el tratamiento del asma pediátrica. Revisión integrativa de la literatura usando las bases de datos: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS y Business Source Complete (EBSCO), utilizando los descriptores: "asma", "pediátrico", "montelukast" y "efectos adversos", unidos por el booleano " Y". Se incluyeron artículos completos, publicados en los últimos 5 años, escritos en portugués, inglés o español, investigados en humanos y relacionados con nuestro objetivo. Se excluyeron aquellos que cumplieron con nuestros criterios de exclusión. Se identificaron cincuenta y tres artículos, de los cuales 11 constituyeron la muestra final de esta revisión. La exposición a montelukast se asoció con una probabilidad 2 veces mayor e reacciones neurosiquiátricas en uno de los artículos analizados, pero los estudios aún no han proporcionado una explicación fisiopatológica común. Las reacciones neurosiquiátricas fueron las más prevalentes, representando más del 90% de la muestra

Evidence-based anti-viral and immunomodulatory potential of Black cumin (Nigella sativa L) in COVID-19 / Potencial antivírico e inmunomodulador en COVID-19 del comino negro (Nigella sativa L) basado en la evidencia

Currently, the whole world is facing a life-threatening novel coronavirus 2019 (COVID-19) pandemic. Natural products are well-known for their potential role against viral disease, and some anti-viral agents have been developed to combat these diseases. Herein, the authors investigated the possible effects of this Holy plant Nigella sativa L. (NS), against coronavirus, using evidence-based and mechanistic approaches to conclude the immune-boosting and alleviation of respiratory systemeffects of NS. The pharmacological studies established a prominent role in treating various respiratory, immune systems, cardiovascular, skin, and gastrointestinal disorders. Literature supported the significant anti-viral role and showed an inhibitory role for NS against MHV-A59 CoV (mouse-hepatitis virus­A59) infected Hela, i.e., HeLaCEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cell. NS is a safe herbal product or dietary supplement and could be an effective and affordable community adjuvant treatment for coronavirus in the current scenario.

Actualmente, el mundo entero se enfrenta a una pandemia del nuevo coronavirus 2019 (COVID-19) que amenaza la vida. Los productos naturales son bien conocidos por su papel potencial contra las enfermedades virales, y se han desarrollado algunos agentes antivirales para combatir estas enfermedades. En este documento, los autores investigaron los posibles efectos de esta planta sagrada Nigella sativa L. (NS), contra el coronavirus, utilizando enfoques mecanicistas y basados en la evidencia para concluir el refuerzo inmunológico y el alivio de los efectos del SN en el sistema respiratorio. Los estudios farmacológicos establecieron un papel destacado en el tratamiento de diversos trastornos respiratorios, del sistema inmunológico, cardiovasculares, cutáneos y gastrointestinales. La literatura apoyó el importante papel antivírico y mostró un papel inhibidor de NS contra células Hela infectadas con MHV-A59 CoV (virus de la hepatitis de ratón-A59), es decir, HeLaCEACAM1a (molécula de adhesión celular 1a relacionada con el antígeno carcinoembrionario epitelial de HeLa). NS es un producto a base de hierbas o un suplemento dietético seguro y podría ser un tratamiento adyuvante comunitario eficaz y asequible para el coronavirus en el escenario actual.

Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos / Adverse drug reactions of montelukast: from theory to practice. Case report

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

Clinical evolution of a severe asthmatics group in the use of immunobiological therapy in a Brazilian Public Hospital

SUMMARY OBJECTIVE: A small portion of the asthmatic population (3.6%) has severe asthma (SA), presenting high morbimortality rates and demanding more financial resources than other asthmatic populations. The use of immunobiological therapy is an effective tool in controlling symptoms, decreasing the number of exacerbations, and reducing the use of systemic corticosteroids in these patients. In Brazil, epidemiological data regarding this asthmatic population using immunobiologicals and their evolution are scarce. METHODS: This is an observational, analytical, cross-sectional, and retrospective study. The sample consisted of adult patients with SA in follow-up at the pulmonology service of the Complexo Hospital de Clínicas of the Federal University of Paraná, from January 2011 to August 2019. The analyzed variables were as follows: the number of exacerbations that required hospitalization in the previous year, forced expiratory volume in one second (FEV1), and asthma control test (ACT) scores before and after the start of immunobiological therapy. RESULTS: We studied 20 patients with SA using omalizumab or mepolizumab. We observed an increase in the mean ACT score of 4.8 points, a nonsignificant reduction in the number of exacerbations that required hospitalization, and a slight improvement in the FEV1. Regarding the patients using chronic systemic corticosteroid therapy, 14.2% (n=1) of patients had the medication discontinued and 57% (n=4) of patients had the dose reduced by half. CONCLUSION: The use of omalizumab and mepolizumab as additional therapy in SA provided a significant improvement in the ACT and allowed the dose reduction of systemic corticosteroids, without significant improvement in FEV1 and in the frequency of severe exacerbations.

Efectos de la suplementación con vitamina D en el control del asma en pacientes adultos: una revisión sistemática / Effects of vitamin D supplementation on asthma control in adult patients: a systematic review

INTRODUCCIÓN: El asma es una enfermedad crónica inflamatoria de la vía aérea e inmunomediada en su patogénesis. La vitamina D es un inmunomodulador que regula el perfil secretor de citoquinas, entre otras funciones celulares. Una asociación entre la suficiencia de vitamina D y mejoría en la función pulmonar, control de asma y número de exacerbaciones se ha propuesto en adultos, importante dada la elevada prevalencia de insuficiencia de vitamina D globalmente. OBJETIVO: Conocer los efectos de la suplementación con vitamina D en el control del asma en adultos. MÉTODOS: Se realizó una revisión sistemática de la literatura a través de una búsqueda en la base de datos PubMed y EMBASE. Los desenlaces primarios fueron cambios en VEF1, control sintomático, frecuencia de exacerbaciones, además de eventos adversos y FEM como desenlaces secundarios. La calidad de evidencia de los desenlaces fue evaluada a través del modelo GRADE. RESULTADOS: Siete estudios fueron seleccionados después de remover duplicados y aplicar los criterios de inclusión y exclusión, con calidad de evidencia muy baja aplicando sistema GRADE. DISCUSIÓN: No se encontraron diferencias estadísticamente significativas tras la suplementación con vitamina D en los desenlaces evaluados en general, pero dada la calidad de evidencia muy baja y que no se reportaron efectos adversos serios, es necesario tomar cautelosamente estos resultados. Asímismo no se puede descartar la utilidad de esta terapia como tratamiento auxiliar a los pacientes asmáticos con este déficit vitamínico.

BACKGROUND: Asthma is an airway chronic disease, with an important inflammatory component within its pathogenesis, driven by a dysregulated immune response. Vitamin D is an immunomodulator that regulates cell proliferation, differentiation and cytokine secretion profile. An association between vitamin D sufficiency and improvement in pulmonary function, asthma control and a decrease in exacerbations have been proposed in the adult population, which falls into importance given the high prevalence of vitamin D insufficiency globally. OBJECTIVE: To know vitamin D supplementation effects in asthma control in adults. METHODS: Through a PubMed and EMBASE database search, a systematic review of the literature was conducted. Primary outcomes were: changes in FEV1, symptomatic control, exacerbation frequency and PEF and adverse events as secondary outcomes. Outcome evidence quality assessment was made using the GRADE model. Results: Seven studies were selected after taking out duplicates, applying inclusion and exclusion criteria. In all cases, evidence quality assessed by the GRADE system yielded very low quality. CONCLUSIONS: No statistically significant differences were found after vitamin D supplementation in the overall evaluated outcomes. Nonetheless, a cautious interpretation of studies is mandatory, because evidence quality was very low and no serious adverse events were reported. Hence this treatment usefulness as an ancillary therapy for vitamin D deficient asthmatic patients cannot be dismissed.

Anti-asthmatic effect of agarwood alcohol extract in mice and its mechanism / 中国中药杂志

As recorded, agarwood has the function of improving qi reception and relieving asthma, but the underlying mechanism is unclear and rarely reported. Therefore, this study explored the anti-asthmatic effect of the alcohol extract of agarwood produced by the whole-tree agarwood-inducing technique(Agar-Wit) in the asthma mouse model induced by intraperitoneal injection of ovalbumin(OVA) + Al(OH)_3 combined with intranasal administration of OVA and the mechanism, and compared the anti-asthmatic effects of agarwood induced with different methods. Firstly, the anti-inflammatory and anti-asthmatic effects of Agar-Wit agarwood in mice were evaluated based on the asthma frequency, lung tissue injury, and peripheral inflammatory white blood cell(WBC) count and eosinophil count. Then, the levels of interleukin-1β(IL-1β), IL-17, and IL-10 in serum of mice were detected by enzyme-linked immunoassay(ELISA) and the expression of inflammation-and apoptosis-related genes in tissues was measured by reverse transcription polyme-rase chain reaction(RT-PCR) so as to preliminarily explore the anti-asthmatic mechanism. RESULTS:: showed that the alcohol extract of Agar-Wit agarwood significantly reduced asthma frequency, relieved pathological injury, improved peripheral WBC count and eosinophil count, decreased the levels of inflammatory cytokines IL-1β and IL-17, elevated the level of anti-inflammatory cytokine IL-10, and down-regulated the mRNA expression of IL-1 R, tumor necrosis factor receptor R(TNFR), nuclear transcription factor-kappa B(NF-κB), Bax, and caspase 3, but had no significant influence on the expression of high-mobility group box 1(HMGB1) protein, caspase 8, and Bcl-2. The effect of Agar-Wit agarwood alcohol extract was better than that of wild agarwood alcohol extract and alcohol extract of agarwood induced with the burning-chisel-drilling method at the same dose. In conclusion, Agar-Wit agarwood can significantly alleviate inflammation and asthma, which is related to its anti-inflammation and anti-apoptosis activity.

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.

Consenso chileno SOCHINEP-SER para el diagnóstico y tratamiento del asma en el escolar / Chilean SOCHINEP-SER consensus for asthma diagnosis and treatment in school age children

Bronchial asthma is the most prevalent chronic condition among children, however, in Chile, it is underdiagnosed. This may be due to medical professionals failing to recognize the disease. It is essential to be aware of the symptoms and signs that are suggestive of the disease in order to begin an appropriate treatment to achieve disease control. Asthma must be suspected in school age children who present repeated episodes of bronchial obstruction. The diagnosis should be confirmed with lung function tests that demonstrate variable airflow obstruction with a positive bronchodilator response. Treatment is based on two fundamental pillars: education and pharmacological treatment. Educational activities must include: information about the disease and its treatment, regular monitoring of treatment adherence, teaching and reviewing the correct inhalation technique at every checkup, developing a personalized written action plan and scheduling regular follow-up appointments. The gold standard for treatment is maintenance inhaled corticosteroids, in the lowest possible dose that enables disease control. The goal of the treatment is to eliminate daily symptoms and asthma crisis. Therapy should be increased if control is not achieved, but before starting it, adherence to maintenance treatment, inhalation technique, presence of associated comorbidities and environmental exposure should be evaluated. In the mild patient, who is not receiving maintenance therapy, rescue treatment should be done with bronchodilators, always associated with inhaled corticosteroids. This consensus is a guide to improve the diagnosis, treatment and control of asthma in schoolchildren.

El asma bronquial es la enfermedad crónica más frecuente en la infancia. Sin embargo en Chile existe un importante subdiagnóstico. Es fundamental estar atentos a los síntomas y signos que nos hacen sospechar el diagnóstico para iniciar un tratamiento oportuno, que asegure un buen control de la enfermedad. Debemos sospechar asma en todo escolar que presente cuadros repetidos de obstrucción bronquial. El diagnóstico debe confirmarse con pruebas de función pulmonar que demuestren obstrucción variable al flujo aéreo y respuesta broncodilatadora positiva. El tratamiento se basa en dos pilares fundamentales: la educación y el tratamiento farmacológico. Las actividades educativas deben incluir contenidos acerca de la enfermedad y su tratamiento, se debe monitorizar constantemente la adherencia al tratamiento de mantención, enseñar la técnica inhalatoria correcta y revisar en cada control, entregar un plan de acción escrito personalizado frente al inicio de una crisis y realizar controles médicos periódicos. Con respecto al tratamiento farmacológico, el estándar de oro es el uso de corticoides inhalados permanentes, en la mínima dosis posible que logre el control de la enfermedad. El objetivo del tratamiento es la supresión de los síntomas diarios y de las crisis. El tratamiento se irá incrementando en la medida que no haya una respuesta adecuada, pero antes de aquello se debe evaluar la adherencia al tratamiento de mantención, la técnica inhalatoria, presencia de comorbilidades asociadas y exposición ambiental. En el paciente leve, que esté sin tratamiento permanente, el rescate debe realizarse con broncodilatadores asociados siempre a un corticoide inhalado. Este consenso es una guía de apoyo para mejorar el diagnóstico oportuno, tratamiento y control del asma en el escolar.

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

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

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

2020 Brazilian Thoracic Association recommendations for the management of asthma / Recomendações para o manejo da asma da Sociedade Brasileira de Pneumologia e Tisiologia - 2020

ABSTRACT The pharmacological management of asthma has changed considerably in recent decades, as it has come to be understood that it is a complex, heterogeneous disease with different phenotypes and endotypes. It is now clear that the goal of asthma treatment should be to achieve and maintain control of the disease, as well as to minimize the risks (of exacerbations, disease instability, accelerated loss of lung function, and adverse treatment effects). That requires an approach that is personalized in terms of the pharmacological treatment, patient education, written action plan, training in correct inhaler use, and review of the inhaler technique at each office visit. A panel of 22 pulmonologists was invited to perform a critical review of recent evidence of pharmacological treatment of asthma and to prepare this set of recommendations, a treatment guide tailored to use in Brazil. The topics or questions related to the most significant changes in concepts, and consequently in the management of asthma in clinical practice, were chosen by a panel of experts. To formulate these recommendations, we asked each expert to perform a critical review of a topic or to respond to a question, on the basis of evidence in the literature. In a second phase, three experts discussed and structured all texts submitted by the others. That was followed by a third phase, in which all of the experts reviewed and discussed each recommendation. These recommendations, which are intended for physicians involved in the treatment of asthma, apply to asthma patients of all ages.

RESUMO O manejo farmacológico da asma mudou consideravelmente nas últimas décadas, com base no entendimento de que a asma é uma doença heterogênea e complexa, com diferentes fenótipos e endótipos. Agora está claro que o objetivo do tratamento da asma deve ser alcançar e manter o controle da doença e evitar riscos futuros (exacerbações, instabilidade da doença, perda acelerada da função pulmonar e efeitos adversos do tratamento). Isso implica em uma abordagem personalizada, incluindo tratamento farmacológico, educação do paciente, plano de ação por escrito, treinamento para uso do dispositivo inalatório e revisão da técnica inalatória a cada visita ao consultório. Um painel de 22 pneumologistas brasileiros foi convidado a revisar criticamente evidências recentes de tratamento farmacológico da asma e a preparar esta recomendação, um guia de tratamento adaptado à nossa realidade. A escolha dos tópicos ou questões relacionadas às mudanças mais significativas nos conceitos e, consequentemente, no manejo da asma na prática clínica foi realizada por um painel de especialistas. Foi solicitado a cada especialista que revisasse criticamente um tópico ou respondesse a uma pergunta, com base em evidências, para estas recomendações. Numa segunda fase, três especialistas discutiram e estruturaram todos os textos submetidos pelos demais e, na última fase, todos revisaram e discutiram cada recomendação. As presentes recomendações se aplicam a adultos e crianças com asma e destinam-se a médicos envolvidos no tratamento da doença.

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Evaluation of smooth muscle relaxant potential of Bismarckia nobilis (Hildebr. & Wendl.) in diarrhea, hypertension and asthma by ex-vivo and in-vivo method / Evaluación del potencial relajante en músculo liso de Bismarckia nobilis (Hildebr. & Wendl.) en diarrea, hipertensión y asma por métodos ex vivo e in vivo

To explore the mechanistic basis behind smooth muscle relaxant prospective of Bismarckia nobilis in gastrointestinal, respiratory and cardiovascular ailments. The methanolic extract of B. nobilis and sub-fractions have been evaluated in vitro rabbit isolated tissues, in vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice. The B. nobilis extract relaxed spontaneous and K+(80 mM)- induced contractions in rabbit isolated jejunum preparations, CCh (1 µM) and K+ (80 mM)-induced contractions in tracheal and bladder preparations, PE (1 µM) and K+ (80 mM)-induced concentrations in aorta preparations, likewise verapamil. Spasmolytic activity of dichloromethane fraction is stronger as compared to aqueous fraction. In vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice further supported spasmolytic activity. B. nobilis extract possess anti-spasmodic, anti-diarrheal, airway relaxant and vasodilator activities possible mediated through calcium channel blocking mechanism, justifying therapeutic utility of B. nobilis in diarrhea, asthma and hypertension.

El objetivo de trabajo fue explorar el mecanismo de acción relacionado con el efecto relajante del músculo liso inducido por Bismarckia nobilis (B. nobilis) en enfermedades gastrointestinales, respiratorias y cardiovasculares. El extracto metanólico de B. nobilis y subfracciones fue evaluado in vitro en tejidos aislados de conejos. Además se evaluó diarrea in vivo inducida con aceite de ricino en ratas y la actividad de harina de carbón vegetal en ratones. El extracto de B. nobilis relajó tanto las contracciones espontáneas como las inducidas por K+(80 mM) en preparaciones de yeyuno aisladas de conejos, las contracciones inducidas por PE (1 µM) y K+(80 mM) inducidas en preparaciones de aorta; de manera similar a verapamilo. La actividad espasmolítica de la fracción de diclorometano es más potente en comparación con la fracción acuosa. La diarrea inducida in vivo por el aceite de ricino en ratas y la actividad de la harina de carbón vegetal en ratones apoyaron aún más la actividad espasmolítica. El extracto de B. nobilis posee actividades antiespasmódicas, antidiarreicas, relajantes de las vías respiratorias y vasodilatadoras, posibles a través del mecanismo de bloqueo de los canales de calcio, lo que justifica la utilidad terapéutica de B. nobilis en la diarrea, el asma y la hipertensión.

Asma: uso adecuado de dispositivos para inhalación / Asthma: correct use of inhalation drug-delivery devices

Resumen La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.

Abstract Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.

Clinical and inflammatory phenotypic features of asthmatic patients sensitive to cold stimulation / 南方医科大学学报

OBJECTIVE@#To explore the clinical symptoms, lung function and airway inflammation phenotype characteristics of asthmatic patients who are sensitive to cold stimulation.@*METHODS@#Eighty patients with newly diagnosed bronchial asthma or with mild to moderate acute exacerbation of previously diagnosed bronchial asthma but without regular treatment were selected. According to whether cold air stimulation could induce respiratory symptoms such as cough and wheeze, the patients were divided into cold-insensitive group (45 cases) and cold-sensitive group (35 cases). All the patients were treated with inhaled corticosteroid (ICS), long-acting β2 receptor agonist (LABA; salmeterol xinafoate and fluticasone propionate powder for inhalation, 50 μg/250 μg, twice daily) and montelukast sodium tablets (10 mg, once daily); short-acting β2 receptor agonist (SABA) and/or systemic glucocorticoid (prednisone acetate tablets, 10 mg, once daily; or injection of methylprednisolone sodium succinate, 40 mg) were given if necessary. Asthma Control Test (ACT) score before treatment and at 3 months of treatment was used to assess the clinical symptoms such as cough and wheeze; spirometry was performed to determine lung function impairment and recovery. Blood and induced sputum cell counts were examined to determine the characteristics of airway inflammation.@*RESULTS@#The two groups were comparable for age, gender, BMI, proportion of smokers and allergic rhinitis before treatment. The cold-sensitive patients experienced significantly more frequent acute exacerbations than the cold-insensitive patient within 1 year before the visit ( < 0.05), but the use of SABA and glucocorticoid for symptom control during the treatment did not differ significantly between the two groups ( > 0.05). The ACT scores of the cold-sensitive group were significantly lower than those of the cold-insensitive group both before and after the treatment ( < 0.01). Compared with the cold-insensitive patients, the cold-sensitive patients had more obvious impairment of FEV1/FVC% and FEV1%pred before treatment ( < 0.01), and also showed poorer recovery after treatment ( < 0.05). The percentages of eosinophils in blood and induced sputum samples did not differ significantly between the two groups either before and after the treatment, but the percentage of neutrophils was significantly higher in the cold-sensitive group ( < 0.01). In the induced sputum samples collected before treatment, the cell populations consisted mainly of eosinophilic subtype (60%) and neutrophilic subtype (20%) in the cold-insensitive group; in the cold-sensitive patients, the sputum neutrophilic subtype cells increased significantly to 42.86% (=0.03) and the eosinophilic subtype cells were lowered to 31.43% (=0.01).@*CONCLUSIONS@#The cold-sensitive asthmatic patients experience frequent recurrent and/or aggravated symptoms and have obvious lung function impairment. Different from that in patients with classic asthma, the airway inflammatory phenotype in these patients is characterized by the domination by neutrophilic subtype.

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.