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1.
Rev Med Liege ; 75(S1): 130-132, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33211435

RESUMO

Given the prominent role of respiratory viruses in asthma exacerbations it has been feared that the SARS-CoV-2 pandemic may result in massive irruption of asthmatic patients in the hospital emergency departments. It seems, however, that asthma is not a particular risk factor for SARS-COV-2 infection nor for death resulting from severe infection. Inhaled corticosteroids (ICS) were found to reduce expression of ACE2 receptor in sputum cells, thereby maybe reducing the risk of lung infection. Only the more severe asthmatic patients treated with oral corticoids or high dose ICS were found to be at risk of death, presumably because of associated comorbidities. Biologicals directed towards IgE or interleukin-5 do not seem to confer an increased risk of severe infection.


Assuntos
Antiasmáticos , Asma , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Administração por Inalação , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Betacoronavirus , Humanos
2.
Respir Res ; 21(1): 265, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050900

RESUMO

BACKGROUND: Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study. METHODS: CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18-75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants' type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit. DISCUSSION: CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation. TRIAL REGISTRATION: NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Idoso , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/diagnóstico , Asma/imunologia , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
4.
Arerugi ; 69(8): 678-682, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32963191

RESUMO

We report the case of a 66-year-old patient with severe asthma complicated by eosinophilic chronic rhinosinusitis (ECRS). The patient was initially treated with benralizumab, which resulted in marked improvement of asthma symptoms and reduced the peripheral blood eosinophil count to 0/µL. Additionally, oral steroids were discontinued. After 7 months of benralizumab administration, the asthma symptoms worsened and peripheral blood eosinophil count increased to 813/µL. The neutralizing antibodies to benralizumab may have resulted in the recurrence of symptoms due to eosinophilic inflammation. The nasal symptoms, on which benralizumab had an unremarkable effect, improved when treatment was switched to mepolizumab. However, the difference in effects of biologics on ECRS has not been elucidated and warrants further investigation. To the best of our knowledge, this is the first report of a case of severe asthma in which mepolizumab administration reversed the clinical deterioration of asthma, which was possibly caused by neutralizing antibodies to benralizumab.


Assuntos
Antiasmáticos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma , Idoso , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Progressão da Doença , Substituição de Medicamentos , Humanos
5.
Dtsch Arztebl Int ; 117(25): 434-444, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32885783

RESUMO

BACKGROUND: Asthma is a chronic inflammatory airway disease that usually causes variable airway obstruction. It affects 5-10% of the German population. METHODS: This review is based on relevant publications retrieved by a selective search, as well as on national and international guidelines on the treatment of mild and moderate asthma in adults. RESULTS: The goal of treatment is to attain optimal asthma control with a minimal risk of exacerbations and mortality, loss of pulmonary function, and drug side effects. This can be achieved with a combination of pharmacotherapy and non-drug treatment including patient education, exercise, smoking cessation, and rehabilitation. Pharmacohterapy is based on inhaled corticosteroids (ICS) and bronchodilators. It is recommended that mild asthma should be treated only when needed, either with a fixed combination of ICS and formoterol or with short-acting bronchodilators. For moderate asthma, maintenance treatment is recommended, with an inhaled fixed combinations of ICS and long-acting beta-mimetics, possibly supplemented with longacting anticholinergic agents. Allergen immunotherapy, i.e., desensitization treatment, should be considered if the allergic component of asthma is well documented and the patient is not suffering from uncontrolled asthma. Asthma control should be monitored at regular intervals, and the treatment should be adapted accordingly. CONCLUSION: The treatment of asthma in adults should be individually tailored, with anti-inflammatory treatment as its main component.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides , Adulto , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Quimioterapia Combinada , Fumarato de Formoterol , Humanos
6.
Lancet Respir Med ; 8(10): 1032-1044, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910897

RESUMO

Severe asthma in children is rare, accounting for only a small proportion of childhood asthma. After addressing modifiable factors such as adherence to treatment, comorbidities, and adverse exposures, children whose disease is not well controlled on high doses of medication form a heterogeneous group of severe asthma phenotypes. Over the past decade, considerable advances have been made in understanding the pathophysiology of severe therapy-resistant asthma in children. However, asthma attacks and hospital admissions are frequent and mortality is still unacceptably high. Strategies to modify the natural history of asthma, prevent severe exacerbations, and prevent lung function decline are needed. Mechanistic studies have led to the development of several biologics targeting type 2 inflammation. This growing pipeline has the potential to reduce the burden of severe asthma; however, detailed assessment and characterisation of each child with seemingly severe asthma is necessary so that the most effective and appropriate management strategy can be implemented. Risk stratification, remote monitoring, and the integration of multiple data sources could help to tailor management for the individual child with severe asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Asma/complicações , Criança , Pré-Escolar , Progressão da Doença , Hospitalização , Humanos
7.
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
8.
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
9.
Medicine (Baltimore) ; 99(35): e21858, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871910

RESUMO

INTRODUCTION: These years, due to dissatisfaction with western medicine treatments, traditional Chinese medicine (TCM) becomes a main treatment for bronchial asthma patients. Lung and kidney yang deficiency syndrome is a common type of asthma and the Chinese herbal medicine formula modified Mahuang-Fuzi-Xixin (MFX) decoction is prescribed for mild bronchial asthma patients with acute exacerbation syndrome. However, there is not obvious evidence to support the efficacy and safety of modified MFX decoction the efficacy and safety to treat mild bronchial asthma and the mechanism of this disease is still unclear. METHODS: A double-blind, placebo-controlled, randomized clinical trial was proposed by us. After a 10-day run-in period, 180 eligible objects will be recruited in this study. These subjects will be allocated to the experimental group or control group in a 1:1 ratio. Patients in the experimental group will take modified MFX decoction. At the same time, patients in the control group will receive a matched placebo. The budesonide inhalation powder will be used as a western medicine treatment for both groups. All subjects will receive 14 days of treatment and another 6 months of follow-up. The primary outcome is the mean change in peak expiratory flow rate from the baseline to 14 days in this research. The secondary outcome includes forced expiratory volume in one second, asthma control test score, Asthma Quality of Life Questionnaire score, curative effect of TCM syndrome, and salbutamol dosage. This trial will also explore the association between the change of immunoglobulin E and modified MFX decoction treatment. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of modified MFX decoction in patients with mild bronchial asthma during acute exacerbation. It also will explore the mechanism of this formula in the treatment of bronchial asthma, which will provide another treatment option for patients with mild bronchial asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Humanos , Pico do Fluxo Expiratório
10.
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
12.
Niger J Clin Pract ; 23(8): 1033-1038, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788477

RESUMO

Background: Inhaler corticosteroids (ICS) are the most commonly used antiinflammatory drugs in the treatment of asthma. Although systemic adverse effects are minimal, patients hesitate to use ICS for a long time because of corticophobia. There is no study evaluating corticophobia via Likert-type appendix among the asthmatic patients. Aim: In this study, it was aimed to evaluate the fears and beliefs about ICS in asthmatic patients. Subjects and Methods: Between December 2017 and January 2018, 150 stable asthmatic patients were included in the study. Demographic data (age, education, smoking history, etc.) and asthma-related data (pulmonary function test, drug use) were recorded. The appendix of TOPICOP study applied to the patients with asthma which was composed of 10 questions (five questions about fear of ICS and five questions about beliefs of ICS). Results: The rate of ICS maintain in stable asthmatic patients was found to be 66.6%. According to the survey results, 68% of the patients believed that ICS may lead to weight gain, 52% believed that ICS may lead to infection, 73% believed that ICS may pass into bloodstream, and 67.3% believed that ICS may damage the lungs. It was also found that 90.7% needed to be informed about ICS and 67.3% wanted to cut the ICS drug as soon as possible. Conclusion: We found that treatment adherence may increase, if physicians allocate more time to asthma patients to inform about ICS beneficial effects at the initiating of ICS treatment and control visits.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medo , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Transtornos Fóbicos/psicologia , Administração por Inalação , Corticosteroides/efeitos adversos , Adulto , Antiasmáticos/efeitos adversos , Asma/psicologia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Transtornos Fóbicos/epidemiologia , Transtornos Fóbicos/etiologia , Inquéritos e Questionários
13.
J Assoc Physicians India ; 68(8): 82-88, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32738847

RESUMO

Epidemiologically the burden of asthma in India is alarming with a median prevalence of 7%. As the symptoms of asthma ascend the severity ladder, the prediction of the cause of asthma is important from the treatment point of view. The GINA 2020 states that the management of asthma should be individualized as per the patient depending on patient phenotype. The goal of asthma treatment is to achieve good control of symptoms, to reduce exacerbations and to improve quality of life. Guidelines recommend adapting the level of treatment to the level of disease severity, and this approach has been demonstrated to be effective in the majority of asthma patients overall. However, it is known that a small but significant proportion of patients do not achieve adequate control despite optimized treatment, and these patients are frequently prescribed high doses of oral steroids in an attempt to achieve control. For patients with severe uncontrolled asthma, monoclonal antibodies (mAbs) against IgE or IL-5 are available as add-on treatments to inhaled corticosteroid (ICS) plus long-acting ß2-agonist (LABA) therapy. With a plethora of available modalities, the fact still remains that there is a large treatment gap and the number of people living with asthma in India is predicted to be around 30 million. This article reviews the phenotypes/endotypes of asthma described in India and the current therapies for management.


Assuntos
Antiasmáticos/uso terapêutico , Asma , Administração por Inalação , Corticosteroides , Quimioterapia Combinada , Humanos , Índia , Qualidade de Vida
14.
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
16.
Ann Allergy Asthma Immunol ; 125(4): 433-439, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629016

RESUMO

BACKGROUND: Asthma is a heterogeneous disease with emerging phenotypes and endotypes. At present, 5 distinct biologics are Food and Drug Administration-approved as an add-on therapy for difficult-to-control type 2-high asthma. Because allergy specialists manage a spectrum of diseases for which biologics may be appropriate, it is important to understand their prescribing patterns. OBJECTIVE: To elucidate the allergist's use of biologics in the treatment of asthma, including barriers, preferences, indications for prescribing, measures to determine effectiveness, and cost-effectiveness. METHODS: A survey was performed among allergists using a semistructured 10-item self-administered web-based questionnaire and the responses were analyzed using one-way frequencies and multiple logistic regression. RESULTS: The response rate was approximately 9%. Omalizumab was the most prescribed biologic for asthma (98%), and "uncontrolled asthma despite adherence to controller medication" was the most common reason. The common selection criteria among the biologics included elevated peripheral eosinophil count, asthma with nasal polyps, and asthma type (type 1; type 2; nonallergic). A decreased exacerbation frequency was the best standard to determine the efficacy among biologics. Benralizumab was considered the most cost-effective. CONCLUSION: This study represents one of the largest surveys among allergy specialists regarding the real-world use of asthma biologics. It seems that there has been reasonably good dissemination and application of current guidelines among allergists based on prescribing patterns. However, their responses reflect the need for the continued modification of asthma guidelines that incorporate novel biologics and other pathway-specific agents into step therapy. As clinical phenotypes and predictive biomarkers develop, allergy specialists will be better prepared to practice precision medicine that optimizes the use of asthma biologics.


Assuntos
Alergistas , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Padrões de Prática Médica , Humanos , Inquéritos e Questionários
19.
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
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