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2.
J Environ Pathol Toxicol Oncol ; 39(3): 213-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865913

RESUMO

Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/imunologia , Asma/metabolismo , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/citologia , Feminino , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória , Triterpenos/administração & dosagem
3.
J Environ Pathol Toxicol Oncol ; 39(3): 225-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865914

RESUMO

Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Aporfinas/uso terapêutico , Asma/tratamento farmacológico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Aporfinas/administração & dosagem , Asma/imunologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Modelos Animais de Doenças , Eosinófilos/citologia , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória
4.
N Z Med J ; 133(1520): 61-72, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994594

RESUMO

AIM: In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Maori and Pacific peoples, populations with worse asthma outcomes. METHOD: The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable. RESULTS: Seventy-two participants (8%) identified as Maori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70). CONCLUSION: The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Maori and Pacific adults compared with New Zealand European/Other.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Quimioterapia Combinada/métodos , Administração por Inalação , Adulto , Antiasmáticos/administração & dosagem , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Estudos de Casos e Controles , Progressão da Doença , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores/normas , Nova Zelândia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Resultado do Tratamento
5.
Cochrane Database Syst Rev ; 8: CD012977, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32767571

RESUMO

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.


Assuntos
Antiasmáticos/uso terapêutico , Asma/terapia , Broncodilatadores/uso terapêutico , Progressão da Doença , Revisões Sistemáticas como Assunto , Doença Aguda , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Aminofilina/administração & dosagem , Aminofilina/efeitos adversos , Antiasmáticos/administração & dosagem , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Viés , Broncodilatadores/administração & dosagem , Criança , Pré-Escolar , Antagonistas Colinérgicos/uso terapêutico , Hélio , Humanos , Lactente , Tempo de Internação , Antagonistas de Leucotrienos/uso terapêutico , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/efeitos adversos , Sulfato de Magnésio/uso terapêutico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Oxigênio/administração & dosagem , Respiração com Pressão Positiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente , Trabalho Respiratório/efeitos dos fármacos
6.
PLoS One ; 15(7): e0236159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702053

RESUMO

Asthma is a common chronic inflammatory disease. Although effective asthma therapies are available, part of asthmatic population do not respond to these treatment options. In this work we present the result of development of CPL302-253 molecule, a selective PI3Kδ inhibitor. This molecule is intended to be a preclinical candidate for dry powder inhalation in asthma treatment. Studies we performed showed that this molecule is safe and effective PI3Kδ inhibitor that can impact many immune functions. We developed a short, 15-day HDM induced asthma mouse model, in which we showed that CPL302-253 is able to block inflammatory processes leading to asthma development in vivo.


Assuntos
Antiasmáticos/administração & dosagem , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Asma/prevenção & controle , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Administração por Inalação , Animais , Antiasmáticos/uso terapêutico , Linhagem Celular , Inaladores de Pó Seco , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Camundongos
7.
PLoS Med ; 17(7): e1003145, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32692744

RESUMO

BACKGROUND: Guidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs. METHODS AND FINDINGS: We used nationwide UK primary care medical records, 2001-2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (long-acting ß2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown (adjusted hazard ratio, 95% CI, p-value: ICS inhaler dose = 0.86, 0.77-0.93, p < 0.001; ICS mean daily = 0.80, 0.74-0.87, p < 0.001; LABA = 1.01, 0.92-1.11, p = 0.87, other add-on = 1.00, 0.91-1.09, p = 0.79) and no increase in reliever prescriptions (adjusted odds ratio, 95% CI, p-value: ICS inhaler dose = 0.99, 0.98-1.00, p = 0.59; ICS mean daily = 0.78, 0.76-0.79, p < 0.001; LABA = 0.83, 0.82-0.85, p < 0.001; other add-on = 0.86, 0.85-0.87, p < 0.001). Prognostic factors to initiate stepdown included medication burden, but not medication side effects. National Health Service (NHS) indicative prices were used for cost estimates. Stepping down medication, either LABAs or ICSs, could save annually around £17,000,000 or £8,600,000, respectively. Study limitations include the possibility that prescribed medication may not have been dispensed or adhered to and the reason for stepdown was not documented. CONCLUSION: In this UK study, we observed that asthma patients were increasingly prescribed higher levels of treatment, often without clear clinical indication for such high doses. Stepping down medication did not adversely affect outcomes and was associated with substantial cost savings.


Assuntos
Antiasmáticos/administração & dosagem , Antiasmáticos/economia , Asma/tratamento farmacológico , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/economia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/economia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Asma/prevenção & controle , Custos de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Reino Unido
9.
Allergol. immunopatol ; 48(2): 124-129, mar.-abr. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-191814

RESUMO

OBJECTIVE: This study aimed to assess the regular use of long-term asthma-control medication and to determine inhaler techniques in asthmatic children. METHODS: The study was conducted on asthmatic children aged 6-18 years. Information on rescue and controller medications was given and the proper inhalation technique was demonstrated. One month later, patients and parents were asked to answer a questionnaire on drug use and to demonstrate their inhaler techniques. RESULTS: One hundred children and/or their parents were interviewed for the study. All of the patients identified long-term asthma-control medications while quick-relief asthma medications were identified by 93% of the patients. Of the patients, 34% described the dose of their quick-relief medication correctly. All steps in the inhalation technique were correctly carried out by 60.6% of patients using a metered-dose inhaler (MDI), 80% of patients using a Turbuhaler, and 58% of patients using a capsule-based dry-powder inhaler (DPI). Of the participants, 73% reported regular use of long-term asthma-control medications. While the mean age of the patients regularly using long-term asthma medications was 9.05 ± 2.5 years, that of patients not compliant with the regular treatment was 10.29 ± 3.26 years (p = 0.04). The most common reason for irregular drug use was forgetting to take the drug. CONCLUSION: Adherence to long-term asthma-control medications tends to be better in younger patients. Since the most common cause of irregular drug use is forgetting to take the drug, repeated training is necessary to ensure asthma control and the successful treatment of asthmatic children


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Asma/tratamento farmacológico , Administração por Inalação , Antiasmáticos/administração & dosagem , Assistência de Longa Duração , Inquéritos e Questionários , Cooperação e Adesão ao Tratamento , Asma/diagnóstico , Estudos Prospectivos , Formas de Dosagem , Inaladores Dosimetrados
12.
PLoS One ; 15(3): e0229241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119686

RESUMO

While genome-wide association studies have identified genes involved in differential treatment responses to inhaled corticosteroids (ICS) in asthma, few studies have evaluated the potential effects of age in this context. A significant proportion of asthmatics experience exacerbations (hospitalizations and emergency department visits) during ICS treatment. We evaluated the interaction of genetic variation and age on ICS response (measured by the occurrence of exacerbations) through a genome-wide interaction study (GWIS) of 1,321 adult and child asthmatic patients of European ancestry. We identified 107 genome-wide suggestive (P<10-05) age-by-genotype interactions, two of which also met genome-wide significance (P<5x10-08) (rs34631960 [OR 2.3±1.6-3.3] in thrombospondin type 1 domain-containing protein 4 (THSD4) and rs2328386 [OR 0.5±0.3-0.7] in human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2)) by joint analysis of GWIS results from discovery and replication populations. In addition to THSD4 and HIVEP2, age-by-genotype interactions also prioritized genes previously identified as asthma candidate genes, including DPP10, HDAC9, TBXAS1, FBXL7, and GSDMB/ORMDL3, as pharmacogenomic loci as well. This study is the first to link these genes to a pharmacogenetic trait for asthma.


Assuntos
Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Proteínas ADAM/genética , Administração por Inalação , Adolescente , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idoso , Antiasmáticos/uso terapêutico , Asma/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Serviço Hospitalar de Emergência , Feminino , Estudo de Associação Genômica Ampla , Histona Desacetilases/genética , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Resultado do Tratamento , Adulto Jovem
13.
J Bras Pneumol ; 46(1): e20190307, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32130345

RESUMO

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.


Assuntos
Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Gerenciamento Clínico , Administração por Inalação , Fatores Etários , Brasil , Humanos , Fatores de Risco , Índice de Gravidade de Doença , Exacerbação dos Sintomas
14.
Rev Mal Respir ; 37(3): 201-204, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32139106

RESUMO

The main purpose of this review is to highlight mitochondria as a new therapeutic target to prevent bronchial smooth muscle (BSM) remodeling in asthma. Severe asthmatic patients, representing 5-10% of all asthmatics, are characterized by an increased BSM mass which is highly correlated with the severity of the disease and the rate of exacerbations. None of the current asthma therapies are effective in reducing BSM remodelling. This review, based on the current literature, reports the role of mitochondria in BSM, particularly in calcium signaling.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Brônquios , Mitocôndrias Musculares/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Animais , Antiasmáticos/administração & dosagem , Asma/metabolismo , Asma/patologia , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/ultraestrutura , Sistemas de Liberação de Medicamentos/métodos , Metabolismo Energético/efeitos dos fármacos , Humanos , Mitocôndrias Musculares/metabolismo , Terapia de Alvo Molecular/tendências , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/ultraestrutura , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Terapias em Estudo/métodos , Terapias em Estudo/tendências
17.
Lancet Respir Med ; 8(5): 461-474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066536

RESUMO

BACKGROUND: Reslizumab 3 mg/kg administered intravenously is approved for the treatment of severe eosinophilic asthma. We assessed the safety and efficacy of subcutaneous reslizumab 110 mg in two trials in patients with uncontrolled severe asthma and increased blood eosinophils. The aim was to establish whether subcutaneous reslizumab 110 mg can reduce exacerbation rates in these patients (study 1) or reduce maintenance oral corticosteroid dose in patients with corticosteroid-dependent asthma (study 2). METHODS: Both studies were randomised, double-blind, placebo-controlled, phase 3 studies. Entry criteria for study 1 were uncontrolled severe asthma, two or more asthma exacerbations in the previous year, a blood eosinophil count of 300 cells per µL or more (including no more than 30% patients with an eosinophil count <400 cells/µL), and at least a medium dose of inhaled corticosteroids with one or more additional asthma controllers. Patients in study 2 had severe asthma, a blood eosinophil count of 300 cells per µL or more, daily maintenance oral corticosteroid (prednisone 5-40 mg, or equivalent), and high-dose inhaled corticosteroids plus another controller. Patients were randomly assigned (1:1) to subcutaneous reslizumab (110 mg) or placebo once every 4 weeks for 52 weeks in study 1 and 24 weeks in study 2. Patients and investigators were masked to treatment assignment. Primary efficacy outcomes were frequency of exacerbations during 52 weeks in study 1 and categorised percentage reduction in daily oral corticosteroid dose from baseline to weeks 20-24 in study 2. Primary efficacy analyses were by intention to treat, and safety analyses included all patients who received at least one dose of study treatment. These studies are registered with ClinicalTrials.gov, NCT02452190 (study 1) and NCT02501629 (study 2). FINDINGS: Between Aug 12, 2015, and Jan 31, 2018, 468 patients in study 1 were randomly assigned to placebo (n=232) or subcutaneous reslizumab (n=236), and 177 in study 2 to placebo (n=89) or subcutaneous reslizumab (n=88). In study 1, we found no significant difference in the exacerbation rate between reslizumab and placebo in the intention-to-treat population (rate ratio 0·79, 95% CI 0·56-1·12; p=0·19). Subcutaneous reslizumab reduced exacerbation frequency compared with placebo in the subgroup of patients with blood eosinophil counts of 400 cells per µL or more (0·64, 95% CI 0·43-0·95). Greater reductions in annual exacerbation risk (p=0·0035) and longer time to first exacerbation were observed for patients with higher trough serum reslizumab concentrations. In study 2, we found no difference between placebo and fixed-dose subcutaneous reslizumab in categorised percentage reduction in daily oral corticosteroid dose (odds ratio for a lower category of oral corticosteroid use in the reslizumab group vs the placebo group, 1·23, 95% CI 0·70-2·16; p=0·47). The frequency of adverse events and serious adverse events with reslizumab were similar to those with placebo in both studies. INTERPRETATION: Fixed-dose (110 mg) subcutaneous reslizumab was not effective in reducing exacerbation frequency in patients with uncontrolled asthma and increased blood eosinophils (≥300 cells/µL), or in reducing the daily maintenance oral corticosteroid dose in patients with oral corticosteroid-dependent severe eosinophilic asthma. Higher exposures than those observed with 110 mg subcutaneous reslizumab are required to achieve maximal efficacy. FUNDING: Teva Branded Pharmaceutical Products R&D.


Assuntos
Antiasmáticos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Asma/tratamento farmacológico , Administração Oral , Adulto , Asma/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eosinofilia/tratamento farmacológico , Eosinófilos/metabolismo , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologia , Glucocorticoides/administração & dosagem , Humanos , Injeções Subcutâneas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Índice de Gravidade de Doença
18.
Respir Med ; 162: 105880, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32056671

RESUMO

BACKGROUND: We should continually improve tools for evaluating asthma. The aim of this study was to evaluate whether the FEV1/FVC ratio in the lower range of normality is associated with worse outcomes in asthmatics without airway obstruction. METHODS: We screened asthmatics at eight clinics. Subjects answered the Asthma Control Questionnaire and underwent spirometry. We assigned individuals without airway obstruction in three groups according to the post bronchodilator FEV1/FVC ratio: lower range of normality, intermediary range of normality and upper range of normality. Asthma outcomes were hospital admission due to asthma during the preceding year, non-controlled asthma symptoms and moderate-high inhaled maintenance therapy need. RESULTS: In subjects from six to 18 years old, the rate of hospital admission was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups but the frequency of non-controlled symptoms of asthma and moderate-high dose of inhaled maintenance therapy need was similar. From 19 to 59 years old, the rate of moderate-high inhaled maintenance therapy need was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups, but the frequency of hospital admissions and non-controlled symptoms of asthma was similar. Above 59 years old, there was no difference in clinical asthma outcomes between lung function groups. CONCLUSIONS: FEV1/FVC ratio in the lower range of normality is a marker of worse clinical outcomes in asthmatics without airway obstruction.


Assuntos
Asma/diagnóstico , Asma/fisiopatologia , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Adolescente , Obstrução das Vias Respiratórias , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Biomarcadores , Criança , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Quimioterapia de Manutenção , Masculino , Prognóstico , Espirometria , Inquéritos e Questionários
19.
Enferm. glob ; 19(57): 1-14, ene. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193645

RESUMO

INTRODUCCIÓN: El asma aparece como una enfermedad inflamatoria crónica de las vías respiratorias y se caracteriza por episodios de obstrucción bronquial reversible pudiendo ser desencadenada por varios factores. Se constituye como la enfermedad infantil más común, una importante causa de internamiento hospitalario y un problema de salud pública. Las directrices internacionales sobre la gestión del asma reconocen que el tratamiento reside en el control actual y en el riesgo de exacerbaciones, basándose en la gestión de los síntomas. En cuanto a la percepción del control del asma infantil, existen discrepancias entre la percepción de los cuidadores y las indicaciones internacionales. OBJETIVOS: Describir y analizar los datos clínicos, sociodemográficos y factores asociados al control del asma infantil. METODOLOGÍA: Estudio metodológico, cuantitativo y transversal, en una muestra de niños, entre los 6 y los 11 años, con asma y cuidadores. El control del asma ha sido evaluado por el instrumento Childhood Asthma Control Test. RESULTADOS: La muestra fue compuesta por 60 niños y cuidadores. 12% (n = 7) de los niños presentan asma no controlada y 53% (n = 32) asma parcialmente controlada. En el 38% (n = 23) de los cuidadores existieron discrepancias entre el grado clasificado mediante las pautas internacionales y su percepción. El análisis de Regresión Logística confirma que los niños con necesidades de terapia inhalatoria de rescate presentan 7 veces mayor probabilidad de que el asma no esté controlada. CONCLUSIÓN: Resulta perentoria la necesidad de aprehender la complejidad de los factores que interfieren en el control del asma, existiendo necesidad de programas de intervención de gestión de síntomas centrados en los cuidadores, en el niño y en las necesidades identificadas


INTRODUÇÃO: A asma apresenta-se como uma doença crónica e inflamatória das vias aéreas caracterizada por episódios de obstrução brônquica reversível podendo ser desencadeada por diversos fatores. Constitui-se como a doença infantil mais comum, uma importante causa de internamento hospitalar e um problema de saúde pública. As diretrizes internacionais sobre a gestão da asma reconhecem que o tratamento reside no controlo atual e no risco de exacerbações, sendo baseados na gestão de sintomas. Relativamente à perceção do controlo da asma infantil, existem discrepâncias entre a perceção dos cuidadores e as indicações internacionais. OBJETIVOS: Descrever e analisar os dados clínicos, sociodemográficos e fatores associados ao controlo da asma infantil. METODOLOGIA: Estudo metodológico, quantitativo e transversal, numa amostra de crianças, entre os 6 e os 11 anos, com asma e cuidadores. O controlo da asma foi avaliado pelo instrumento Childhood Asthma Control Test. RESULTADOS: A amostra foi composta por 60 crianças e cuidadores. 12% (n=7) das crianças apresentam asma não controlada e 53% (n=32) asma parcialmente controlada. Em 38% (n=23) dos cuidadores existiram discrepâncias entre o grau classificado mediante as guidelines internacionais e a sua perceção. A análise de Regressão Logística confirma que as crianças com necessidades de terapêutica inalatória de resgate apresentam 7 vezes maior probabilidade da asma estar não controlada. CONCLUSÃO: Torna-se perentório a necessidade de apreensão da complexidade dos fatores que interferem no controlo da asma, existindo necessidade de programas de intervenção de gestão de sintomas centrados nos cuidadores, na criança e nas necessidades identificadas


INTRODUCTION: Asthma is an airways chronic and inflammatory disease characterized by episodes of reversible bronchial obstruction and can be triggered by several factors. It is the most common childhood disease, an important hospitalization cause and a public health problem. International guidelines of asthma management recognize that treatment based on current management and exacerbations risk, which are based on symptom management. Regarding the control perception of childhood asthma, there are discrepancies between the caregiver's perception and the international indications. OBJECTIVES: To describe and analyze the clinical, sociodemographic and factors associated with childhood asthma control. METHODOLOGY: Methodological, quantitative and transversal study, in a sample of 60 children, between 6 and 11 years, and caregivers. Asthma control was evaluated by the instrument childhood Asthma Control Test. RESULTS: The sample consisted of 60 children and caregivers. 12% (n = 7) of the children had uncontrolled asthma, 53% (n = 32) partly controlled asthma. In 38% (n = 23) of the caregivers there were discrepancies between the grade classified through the international guidelines and their perception. Logistic Regression analysis confirms that children with inhalational rescue therapy needs 7 times more likely asthma to be uncontrolled. CONCLUSION: The complexity of the factors that interfere in the control of asthma is urgent and there is a need for symptom management intervention programs focused on the caregivers, the child and the identified needs


Assuntos
Humanos , Masculino , Feminino , Criança , Asma/prevenção & controle , Cuidadores/educação , Antiasmáticos/administração & dosagem , Cuidados de Enfermagem/métodos , Asma/enfermagem , Asma/fisiopatologia , Estudos Transversais , Índice de Gravidade de Doença , Administração por Inalação , Avaliação de Sintomas/métodos , Psicometria/instrumentação
20.
Pneumologie ; 74(2): 103-111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31935761

RESUMO

In the EU, five biologics have been approved as add-on therapy for patients with severe asthma. Until recently, none of the biologics was approved for home use and had to be administered under medical supervision, a time-consuming schedule for both patients and physicians, accompanied by greater expenditure. However, over the last year, four out of the five biologics have been granted approval for patient self-administration at home. The objective of this multiple-choice survey was to understand how patients with severe asthma treated with omalizumab and their treating physicians view the potential home use of biologics exemplified by omalizumab. The questionnaires were answered by 120 physicians and 432 patients (response rate: 51.7 % and 20.6 %, respectively). Overall, 44.7 % of patients were in favour of self-administration at home while 30.6 % opposed this method of administration and 23.8 % of patients were neutral. Especially teenagers and young adults had a positive attitude towards self-administration. 76.7 % of the questioned physicians were in favour of home use for certain patients. Time saving was the main advantage for self-administration mentioned by patients (53.2 %) as well as by physicians (72.5 %). The main concern for patients was 'making a mistake while injecting' (43.8 %) while 'forgetting to inject omalizumab' (73.3 %) was the main concern for physicians. 44.4 % of patients expressed a wish for individual training and 70.8 % of physicians agreed with this statement. The latter group also considered a starter kit including several information materials (54.2 %) as well as an electronic reminder system (50.8 %) as useful. In conclusion, self-administration of biologics has the potential to be timesaving for both patients and physicians.


Assuntos
Antialérgicos/administração & dosagem , Antiasmáticos/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Omalizumab/administração & dosagem , Autoadministração , Adolescente , Adulto , Antialérgicos/uso terapêutico , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Produtos Biológicos/uso terapêutico , Pesquisas sobre Serviços de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inquéritos e Questionários , Adulto Jovem
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