Trends in oral corticosteroids use in severe asthma: a 14-year population-based study.

BACKGROUND: Oral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort. METHODS: We used administrative health databases of British Columbia, Canada (2000-2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression. RESULTS: 21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis. CONCLUSIONS: This population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.

Objectives for algorithmic decision-making systems in childhood asthma: Perspectives of children, parents, and physicians.

Objectives: To identify with children, parents and physicians the objectives to be used as parameters for algorithmic decision-making systems (ADMSs) adapting treatments in childhood asthma. Methods: We first conducted a qualitative study based on semi-structured interviews to explore the objectives that children aged 8-17 years, their parents, and their physicians seek to achieve when taking/giving/prescribing a treatment for asthma. Following the grounded theory approach, each interview was independently coded by two researchers; reconciled codes were used to assess code frequency, categories were defined, and the main objectives identified. We then conducted a quantitative study based on questionnaires using these objectives to determine how children/parents/physicians ranked these objectives and whether their responses were aligned. Results: We interviewed 71 participants (31 children, 30 parents and 10 physicians) in the qualitative study and identified seven objectives associated with treatment uptake and five objectives associated with treatment modalities. We included 291 participants (137 children, 137 parents, and 17 physicians) in the quantitative study. We found little correlation between child, parent, and physician scores for each of the objectives. Each child's asthma history influenced the choice of scores assigned to each objective by the child, parents, and physician. Conclusion: The identified objectives are quantifiable and relevant to the management of asthma in the short and long term. They can therefore be incorporated as parameters for future ADMS. Shared decision-making seems essential to achieve consensus among children, parents, and physicians when choosing the weight to assign to each of these objectives.

Are biological drugs effective and safe in older severe asthmatics?

INTRODUCTION: The treatment of asthma in older ages follows the recommendations of international guidelines for the management of asthma in younger ages, although older age has always represented an exclusion criterion for eligibility to pharmacological trials. This poses a clinical challenge when deciding whether elderly severe asthmatics are candidates for biological drugs. AREAS COVERED: The current article has a narrative structure to review the current literature on efficacy and safety of novel pharmacological drugs against immunoglobulins and interleukins that mediate and orchestrate the main inflammatory pathways in severe asthma, in order to explore whether older subjects (i.e. > 65 years of age) are included. EXPERT OPINION: Asthma in older ages is not a rare entity, and loss of symptom control is common in most advanced ages. Current evidence from randomized clinical trials (RCTs) on the safety of biological drugs in elderly asthmatics is scarce and does not allow drawing definitive conclusions. An urgent call for studies specifically designed for elderly populations is needed, with the purpose to assess the efficacy and safety of target biological therapies in advanced ages. We envision the design of large multi-center clinical trials to decide whether and when geriatric population could benefit from biological therapies.

Beta-blocker use is an independent risk factor for thunderstorm asthma.

OBJECTIVE: To identify risk factors for thunderstorm asthma (TA) in subjects ≥15 years of age from information available in routine clinical records. METHODS: Retrospective and hospital-based case-control study of various clinical factors in all TA cases (n = 53) who presented to a single-site ED in November 2016 (TA16) and in a control group of patients (n = 156) who presented to the same ED with asthma during the pollen season over eight non-TA years. Bivariate analysis and multivariable logistic regression modelling was performed to calculate the odds of TA asthma in the presence of potential risk factors. RESULTS: A logistic regression model revealed that the odds of TA were lower for age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95-0.99), higher for Asian country of birth (OR 4.09, 95% CI 1.40-11.95) and higher for oral beta-blocker use (OR 6.43, 95% CI 1.58-26.33) compared to controls. No difference was found between TA16 cases and controls for allergies (to medication, grass pollen, animal), hayfever, smoking, oral non-steroidal anti-inflammatory drugs, or aspirin. Newly diagnosed asthma was higher in TA16 cases versus controls (32.1% vs 12.2%, P = 0.001). CONCLUSIONS: Oral beta-blocker medications, younger age and Asian-born heritage are risk factors for TA. Further study is required to explore the potential association between beta-blockers and TA.

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

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

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

Trends in asthma mortality in the 0- to 4-year and 5- to 34-year age groups in Brazil / Tendências da mortalidade da asma nas faixas etárias de 0 a 4 anos e 5 a 34 anos no Brasil

ABSTRACT Objective: To provide an update on trends in asthma mortality in Brazil for two age groups: 0-4 years and 5-34 years. Methods: Data on mortality from asthma, as defined in the International Classification of Diseases, were obtained for the 1980-2014 period from the Mortality Database maintained by the Information Technology Department of the Brazilian Unified Health Care System. To analyze time trends in standardized asthma mortality rates, we conducted an ecological time-series study, using regression models for the 0- to 4-year and 5- to 34-year age groups. Results: There was a linear trend toward a decrease in asthma mortality in both age groups, whereas there was a third-order polynomial fit in the general population. Conclusions: Although asthma mortality showed a consistent, linear decrease in individuals ≤ 34 years of age, the rate of decline was greater in the 0- to 4-year age group. The 5- to 34-year group also showed a linear decline in mortality, and the rate of that decline increased after the year 2004, when treatment with inhaled corticosteroids became more widely available. The linear decrease in asthma mortality found in both age groups contrasts with the nonlinear trend observed in the general population of Brazil. The introduction of inhaled corticosteroid use through public policies to control asthma coincided with a significant decrease in asthma mortality rates in both subsets of individuals over 5 years of age. The causes of this decline in asthma-related mortality in younger age groups continue to constitute a matter of debate.

RESUMO Objetivo: Apresentar uma atualização das tendências da mortalidade da asma no Brasil em duas faixas etárias: 0-4 anos e 5-34 anos Métodos: Dados relativos ao período de 1980 a 2014 referentes à mortalidade da asma, conforme se definiu na Classificação Internacional de Doenças, foram extraídos Sistema de Informação sobre Mortalidade do Departamento de Tecnologia da Informação do Sistema Único de Saúde. Para analisar as tendências temporais das taxas padronizadas de mortalidade da asma, realizou-se um estudo ecológico de séries temporais com modelos de regressão para as faixas etárias de 0 a 4 anos e 5 a 34 anos Resultados: Houve uma tendência linear de redução da mortalidade da asma em ambas as faixas etárias e uma tendência polinomial de terceira ordem na população geral Conclusões: Embora a mortalidade da asma tenha apresentado redução linear consistente em indivíduos com idade ≤ 34 anos, a taxa de declínio foi maior na faixa etária de 0 a 4 anos. A faixa etária de 5 a 34 anos também apresentou redução linear da mortalidade, e essa redução tornou-se mais pronunciada após o ano de 2004, quando o tratamento com corticosteroides inalatórios tornou-se mais amplamente disponível. A redução linear da mortalidade da asma em ambas as faixas etárias contrasta com a tendência não linear observada na população geral do Brasil. A introdução do uso de corticosteroides inalatórios por meio de políticas públicas de controle da asma coincidiu com uma diminuição significativa das taxas de mortalidade da asma em ambos os subgrupos de indivíduos com mais de 5 anos de idade. As causas dessa redução da mortalidade da asma em faixas etárias mais jovens ainda são objeto de debate.

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.

The effect of Brassica rapa L-Polysaccharide on inflammatory response with asthmatic rats / 中国医师杂志

Objective To investigate the effect of Brassica rapa L-Polysaccharide on inflammatory response with asthmatic rats.Methods Forty Wistar rats were randomly divided into normal control group,model group,low-dose group and turnip large-dose group of Brassica rapa L.extract.The rats of model group,low-dose group and turnip large-dose group of Brassica rapa L-Polysaccharide were made into the model of asthma.The rats of low-dose group and turnip large-dose group of Brassica rapa L-Polysaccharide were given Brassica rapa L-Polysaccharide from gavage with 5 mg/kg and 2.5.mg/kg,and the rats of normal control group and model group were given distilled water,lasting two weeks.The serum inflammatory factor levels and bronchoalveolar lavage fluid (BALF) cell number of each group of asthmatic rats was detected.Results The serum levels of TNF-alpha,IL-6,IL-2 and CRP of low-dose and high-dose groups of asthmatic rats were significantly lower than the model control group[(90.33 ± 5.90)pg/ml,(92.01 ± 3.26)pg/ml vs (136.43 ± 7.81) pg/ml; (19.08 ± 1.27) pg/ml,(18.33 ± 2.09) pg/ml vs (25.14 ± 2.31) pg/ml;(115.36 ± 7.27) pg/ml,(110.72 ± 10.05) pg/ml vs (193.16 ± 12.33) pg/ml ; (70.58 ± 14.85) μg,/ml,(71.69 ± 12.11) μg/ml vs (93.21 ± 17.25) μg/ml],with a statistically significant difference (t =3.144～ 17.188,P ＜0.01) ; The total cells,eosinophils ratio and proportion of BALF lymphocytes of low-dose and high-dose groups of asthmatic rats were significantly lower than the control group[(1.58 ± 0.67) × 109/L,(1.55 ±0.89)×109/L vs (3.05 ±1.21) × 109/L;(20.31 ±4.27)％,(21.06±3.53)％ vs (26.35± 5.91) ％ ; (16.77 ± 5.47) ％,(15.89 ± 6.03) ％ vs (23.56 ± 4.81) ％],with a statistically significant difference(t =2.430 ～ 3.158,P ＜ 0.05,P ＜ 0.01).Conclusions The Brassica rapa L.Polysaccharide can effectively inhibit the secretion of various inflammatory factors in rats of asthma,and inflammatory response occurred.