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.

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.

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.

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.

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

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

Crisis de asma en pediatría / Asthma crisis in pediatrics

La crisis de asma es el conjunto de síntomas, signos físicos y de laboratorio que apuntan a un aumento de la resistencia al flujo aéreo y como consecuencia la obstrucción bronquial. Es una causa frecuente de consulta y muchas veces la forma como se hace evidente la enfermedad en los pacientes y sus padres. En esta revisión entregamos algunas recomendaciones de cómo reconocer y responder rápidamente a esta situación. Los objetivos primarios al enfrentar una crisis son corregir la hipoxemia, obtener la bronco dilatación y disminuir el riesgo de recaídas. Para lograrlos, debe reconocer rápidamente la hipoxemia y aportar oxígenos suplementario, demostrar la obstrucción de la vía aérea (por clínica y/o laboratorio) y tratarla con broncodilatadores de acción rápida y corticoides sistémicos y una vez manejada la crisis dejar indicaciones suficientes para evitar que esto vuelva a ocurrir.

The asthma crisis is a group of symptoms, with physical and laboratory signs that show an increase in resistance to airflow because of the bronchial obstruction. It is a frequent cause of consultation and It is an often way that the disease becomes evident in patients and their parents. In this review we give some recommendations on how to recognize and have a quickly response to this situation. The primary objectives in facing a crisis are correcting hypoxemia, obtain broncho dilatation and decrease the risk of relapse. In order to achieve this, you should promptly recognize hypoxemia, provide supplemental oxygen, demonstrate airway obstruction (by clinic and / or laboratory) and treat it with rapid-acting bronchodilators and systemic corticosteroids and once the crisis is handled, leave sufficient indications to avoid this to happen again

Tratamiento del asma severo con omalizumab: experiencia pediátrica en Chile y revisión de la literatura / Omalizumab treatment on severe asthma patients: pediatric experience in Chile and literature review

This paper presents clinical experience with Omalizumab treatment in 8 pediatric patients in Chile. All children presented difficult to control asthma despite receiving high intensity treatment, with low quality of life. All patients were studied in order to discard errors in asthma diagnosis and to evaluate asthma treatment adherence and inhalation technique. After evaluation, patients proven to have severe therapy resistant asthma were indicated treatment with Omalizumab. Significant clinical improvement was observed, with reduced asthma symptoms and number of exacerbations, as well as an improved quality of life. Omalizumab showed a good safety profile with mild and transient adverse reactions in 6 administrations of a total of 122.

Se presenta la experiencia clínica con el uso de Omalizumab en 8 pacientes pediátricos en nuestro país. Todos los pacientes presentaban asma sin control a pesar de recibir terapia de alta intensidad, asociado a una muy deficiente calidad de vida. La totalidad de los pacientes fueron sometidos en cada centro a un estudio exhaustivo para poder descartar error en el diagnóstico y se evaluó la adherencia y la técnica inhalada. Al comprobarse que estos pacientes tenían asma severo resistente a tratamiento se indicó Omalizumab, el cual produjo una mejoría clínica significativa. Se observó una reducción de las exacerbaciones y de los síntomas de asma acompañado de una mejoría de la calidad de vida, asociado a un buen perfil de seguridad. Se observaron reacciones adversas leves y transitorias en 6 administraciones de un total de 122.

Tratamento atual de crianças com asma crítica e quase fatal / Contemporary treatment of children with critical and near-fatal asthma

RESUMO A asma é a mais comum das doenças da infância. Embora a maioria das crianças com exacerbações agudas de asma não demanda cuidados críticos, algumas delas não respondem ao tratamento padrão e necessitam de cuidados mais intensos. Crianças com asma crítica ou quase fatal precisam de monitoramento estrito quanto à deterioração e podem requerer estratégias terapêuticas agressivas. Esta revisão examinou as evidências disponíveis que dão suporte a terapias para asma crítica e quase fatal, e resumiu o cuidado clínico atual para essas crianças. O tratamento típico inclui uso parenteral de corticosteroides e fármacos beta-agonistas, por via inalatória ou intravenosa. Para crianças com resposta inadequada ao tratamento padrão, pode-se lançar mão do uso inalatório de brometo de ipratrópio ou intravenoso de sulfato de magnésio, metilxantinas e misturas gasosas com hélio, além de suporte ventilatório mecânico não invasivo. Pacientes com insuficiência respiratória progressiva se beneficiam de ventilação mecânica com uma estratégia que emprega grandes volumes correntes e baixas frequências do ventilador, para minimizar a hiperinsuflação dinâmica, o barotrauma e a hipotensão. Sedativos, analgésicos e bloqueadores neuromusculares são frequentemente necessários na fase inicial do tratamento para facilitar um estado de hipoventilação controlada e hipercapnia permissiva. Pacientes que não conseguem melhorar com a ventilação mecânica podem ser considerados para abordagens menos comuns, como inalação de anestésicos, broncoscopia e suporte extracorpóreo à vida. Esta abordagem atual resultou em taxas de mortalidade extremamente baixas, mesmo em crianças com necessidade de suporte mecânico.

ABSTRACT Asthma is the most common chronic illness in childhood. Although the vast majority of children with acute asthma exacerbations do not require critical care, some fail to respond to standard treatment and require escalation of support. Children with critical or near-fatal asthma require close monitoring for deterioration and may require aggressive treatment strategies. This review examines the available evidence supporting therapies for critical and near-fatal asthma and summarizes the contemporary clinical care of these children. Typical treatment includes parenteral corticosteroids and inhaled or intravenous beta-agonist drugs. For children with an inadequate response to standard therapy, inhaled ipratropium bromide, intravenous magnesium sulfate, methylxanthines, helium-oxygen mixtures, and non-invasive mechanical support can be used. Patients with progressive respiratory failure benefit from mechanical ventilation with a strategy that employs large tidal volumes and low ventilator rates to minimize dynamic hyperinflation, barotrauma, and hypotension. Sedatives, analgesics and a neuromuscular blocker are often necessary in the early phase of treatment to facilitate a state of controlled hypoventilation and permissive hypercapnia. Patients who fail to improve with mechanical ventilation may be considered for less common approaches, such as inhaled anesthetics, bronchoscopy, and extracorporeal life support. This contemporary approach has resulted in extremely low mortality rates, even in children requiring mechanical support.

Asthma treatment in children and adolescents in an urban area in southern Brazil: popular myths and features / Mitos populares e características do tratamento da asma em crianças e adolescentes de zona urbana do sul do Brasil

Objective: To describe the frequency of popular myths about and features of asthma treatment in children and adolescents in an urban area in southern Brazil. Methods: The parents or legal guardians of public school students (8-16 years of age) completed a specific questionnaire regarding their understanding of asthma, asthma control, and treatment characteristics. The sample included parents or legal guardians of students with asthma (n = 127) and healthy controls (n = 124). Results: The study involved 251 parents or legal guardians, of whom 127 (68.5%) were the mothers and 130 (51.8%) were White. The mean age of these participants was 38.47 ± 12.07 years. Of the participants in the asthma and control groups, 37 (29.1%) and 26 (21.0%), respectively, reported being afraid of using asthma medications, whereas 61 (48%) and 56 (45.2%), respectively, believed that using a metered dose inhaler can lead to drug dependence. However, only 17 (13.4%) and 17 (13.7%) of the participants in the asthma and control groups, respectively, reported being afraid of using oral corticosteroids. In the asthma group, 55 students (43.3%) were diagnosed with uncontrolled asthma, only 41 (32.3%) had a prescription or written treatment plan, and 38 (29.9%) used asthma medications regularly. Conclusions: Popular myths about asthma treatment were common in our sample, as were uncontrolled asthma and inappropriate asthma management. Further studies in this field should be conducted in other developing countries, as should evaluations of pediatric asthma treatment programs in public health systems.

Objetivo: Descrever a frequência de mitos populares e as características do tratamento em asma em crianças e adolescentes em uma amostra urbana no sul do Brasil. Métodos: Foi aplicado um questionário específico, contendo perguntas sobre entendimento da doença, controle da asma e características do tratamento a pais/responsáveis de escolares da rede pública (8-16 anos de idade) com diagnóstico de asma (n = 127) e de controles saudáveis (n = 124). Resultados: Participaram do estudo 251 pais/responsáveis, com predomínio de mães como acompanhantes dos escolares (n = 127; 68,5%) e de etnia caucasiana (n = 130; 51,8%), com média de idade de 38,47 ± 12,07 anos. Sobre os mitos, 37 (29,1%) dos participantes do grupo asma e 26 (21,0%) dos do grupo controle relataram possuir receio de utilizar medicamentos para asma, e 61 (48%) e 56 (45,2%), respectivamente, acreditam que os inaladores pressurizados podem levar a dependência ao fármaco. No entanto, apenas 17 (13,4%) dos participantes do grupo asma e 17 (13,7%) dos do grupo controle relataram ter receio de utilizar corticoide oral. A ausência de controle da asma foi detectada em 55 (43,3%) dos escolares no grupo asma, apenas 41 (32,3%) possuíam uma receita ou um plano por escrito de como tratar da asma e 38 (29,9%) fazia uso contínuo de medicamentos para a doença. Conclusões: A presença de mitos populares sobre o tratamento da asma, a falta de controle da doença e seu manejo inadequado mostraram ser elevados nesta amostra. Nossos achados apontam para a necessidade de novos estudos nesse campo em países em desenvolvimento e de uma avaliação dos programas de manejo da asma pediátrica na saúde pública.

Factors associated with quality of life in patients with severe asthma: the impact of pharmacotherapy / Fatores associados à qualidade de vida sob a perspectiva da terapia medicamentosa em pacientes com asma grave

ABSTRACT OBJECTIVE: To identify, characterize, and quantify associations of various factors with quality of life (QoL) in patients with asthma, according to the pharmacotherapy employed. METHODS: This was a cross-sectional study involving 49 patients (≥ 18 years of age) with severe uncontrolled or refractory asthma treated at a specialized outpatient clinic of the Brazilian Unified Health Care System, regularly using high doses of inhaled corticosteroids (ICs) or other medications, and presenting comorbidities. At a single time point, QoL was assessed with the Asthma Quality of Life Questionnaire (AQLQ). The overall AQLQ score and those of its domains were correlated with demographic variables (gender and age); Asthma Control Questionnaire score; pharmacotherapy (initial IC dose, inhaler devices, and polytherapy); and comorbidities. RESULTS: Better AQLQ scores were associated with asthma control-overall (OR = 0.38; 95% CI: 0.004-0.341; p < 0.001), "symptoms" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001), and "emotional function" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001)-and with IC dose ≤ 800 µg-"activity limitation" domain (OR = 0.249; 95% CI: 0.070-0.885; p = 0.029). Worse AQLQ scores were associated with polytherapy-"activity limitation" domain (OR = 3.651; 95% CI: 1.061-12.561; p = 0.036)-and number of comorbidities ≤ 5-"environmental stimuli" domain (OR = 5.042; 95% CI: 1.316-19.317; p = 0.015). CONCLUSIONS: Our results, the importance of this issue, and the lack of studies taking pharmacotherapy into consideration warrant longitudinal studies to establish a causal relationship between the identified factors and QoL in asthma patients.

RESUMO OBJETIVO: Identificar, caracterizar e medir a associação de fatores relacionados à qualidade de vida (QV) de pacientes asmáticos sob a perspectiva da farmacoterapia. MÉTODOS: Estudo de corte transversal com 49 pacientes (≥ 18 anos) portadores de asma grave não controlada ou asma refratária, atendidos em um ambulatório especializado do Sistema Único de Saúde, em uso regular de altas doses de corticoides inalatórios (CIs) e/ou de diversos medicamentos e com comorbidades. Obtiveram-se as medidas de QV através da aplicação do questionário Asthma Quality of Life Questionnaire (AQLQ) num único momento. O escore global e dos domínios do AQLQ foram relacionados com variáveis demográficas (gênero e idade), escore do Asthma Control Questionnaire, terapia medicamentosa (dose inicial de CI, dispositivos inalatórios e politerapia) e comorbidades. RESULTADOS: Melhores escores do AQLQ associaram-se com asma controlada - escore global (OR = 0,38; IC95%: 0,004-0,341; p < 0,001) e domínios "sintomas" (OR = 0,086; IC95%: 0,016-0,476; p = 0,001) e "função emocional" (OR = 0,086; IC95%: 0,016-0,476; p = 0,001) - e com dose de CI ≤ 800 µg - domínio "limitação de atividades" (OR = 0,249; IC95%: 0,070-0,885; p = 0,029). Piores escores do AQLQ correlacionaram-se com politerapia - domínio "limitação de atividades" (OR = 3,651; IC95%: 1,061-12,561; p = 0,036) - e com número de comorbidades ≤ 5 - domínio "estímulo ambiental" (OR = 5,042; IC95%: 1,316-19,317; p = 0,015). CONCLUSÕES: Nossos resultados, a importância do tema, e a escassez de estudos sob a perspectiva da farmacoterapia apontam a necessidade da realização de estudos longitudinais para se estabelecer uma relação de causalidade entre os fatores identificados e a QV em pacientes com asma.

Clinical characteristics of children and adolescents with severe therapy-resistant asthma in Brazil / Características clínicas de crianças e adolescentes brasileiros com asma grave resistente a terapia

AbstractObjective: To describe the clinical characteristics, lung function, radiological findings, and the inflammatory cell profile in induced sputum in children and adolescents with severe therapy-resistant asthma (STRA) treated at a referral center in southern Brazil.Methods: We retrospectively analyzed children and adolescents (3-18 years of age) with uncontrolled STRA treated with high-dose inhaled corticosteroids and long-acting β2 agonists. We prospectively collected data on disease control, lung function, skin test reactivity to allergens, the inflammatory cell profile in induced sputum, chest CT findings, and esophageal pH monitoring results.Results: We analyzed 21 patients (mean age, 9.2 ± 2.98 years). Of those, 18 (86%) were atopic. Most had uncontrolled asthma and near-normal baseline lung function. In 4 and 7, induced sputum was found to be eosinophilic and neutrophilic, respectively; the inflammatory cell profile in induced sputum having changed in 67% of those in whom induced sputum analysis was repeated. Of the 8 patients receiving treatment with omalizumab (an anti-IgE antibody), 7 (87.5%) showed significant improvement in quality of life, as well as significant reductions in the numbers of exacerbations and hospitalizations.Conclusions: Children with STRA present with near-normal lung function and a variable airway inflammatory pattern during clinical follow-up, showing a significant clinical response to omalizumab. In children, STRA differs from that seen in adults, further studies being required in order to gain a better understanding of the disease mechanisms.

ResumoObjetivo: Descrever as principais características clínicas, a função pulmonar, as características radiológicas e o perfil inflamatório do escarro induzido de crianças e adolescentes com asma grave resistente a terapia (AGRT) tratados em um centro de referência do sul do Brasil.Métodos: Foram analisadas retrospectivamente crianças e adolescentes de 3-18 anos com diagnóstico de AGRT não controlada acompanhados durante pelo menos 6 meses e tratados com doses elevadas de corticoide inalatório associado a um β2-agonista de longa duração. Foram coletados prospectivamente dados relativos ao controle da doença, função pulmonar, teste cutâneo para alérgenos, perfil inflamatório do escarro induzido, TC de tórax e pHmetria esofágica.Resultados: Foram analisados 21 pacientes (média de idade: 9,2 ± 2,98 anos). Dos 21, 18 (86%) eram atópicos. A maioria apresentava asma não controlada e função pulmonar basal próxima do normal. Em 4 e 7 pacientes, o escarro induzido revelou-se eosinofílico e neutrofílico, respectivamente, e 67% dos pacientes que repetiram o exame apresentaram mudança no perfil inflamatório. Dos 8 pacientes que receberam omalizumabe (um anticorpo anti-IgE), 7 (87,5%) apresentaram melhora importante da qualidade de vida, com redução importante das exacerbações e hospitalizações.Conclusões: Crianças com AGRT apresentam função pulmonar próxima do normal e padrão inflamatório das vias aéreas variável durante o seguimento clínico, com importante resposta clínica ao omalizumabe. A AGRT em crianças difere da AGRT em adultos, e são necessários mais estudos para esclarecer os mecanismos da doença.