Inhaled corticosteroids in children with persistent asthma : effects of different drugs and delivery devices on growth (review)

Background Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians. Objectives To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma. Search methods We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials. gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019. Selection criteria We selected parallel-group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma. Data collection and analysis At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta-analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs) as the metrics for treatment effects, and the random-effects model for meta-analyses. We did not perform planned subgroup analyses due to there being too few included trials. Main results We included six randomized trials involving 1199 children aged from 4 to 12 years (per-protocol population: 1008), with mild-to-moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months. One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence). Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon- metered dose inhaler (CFC-MDI) at an equivalent dose (MD-0.44 cm/year, 95% CI -1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence). Authors' conclusions This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head-to-head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real-life observational studies seem more attractive and feasible

Mortalidade por asma em crianças brasileiras de até 19 anos de idade no período entre 1980 a 2007

OBJETIVO: Avaliar a tendência de mortalidade por asma em crianças brasileiras de até 19 anos de idade no período de 1980 a 2007. MÉTODOS: Foi realizado um estudo ecológico, de séries temporais, baseado em banco de dados do Departamento de Informática do Sistema Único de Saúde, do qual foi extraído o número de óbitos por asma e a população residente de até 19 anos de idade no país como um todo. O coeficiente de mortalidade foi calculado pelo número de óbitos por asma dividido pela população, multiplicando por 100.000. Utilizou-se o teste de regressão linear para avaliar a tendência temporal de mortalidade. Para a análise, estudaram-se separadamente três grupos etários: 1 a 4 anos, 5 a 9 anos e 10 a 19 anos. RESULTADOS: No período estudado, ocorreram 9.051 óbitos por asma no Brasil em menores de 19 anos. Destes, 69% (6.270 registros) foram de menores de 5 anos. Observou-se um decréscimo significativo de mortalidade por asma no período em todos os grupos etários. A redução média anual do coeficiente de mortalidade por asma em crianças foi de 0,022 (p < 0,0001). De 1 a 4 anos foi de 0,076, de 5 a 9 anos foi de 0,005, e de 10 a 19 anos foi de 0,004 (p < 0,0001). CONCLUSÃO: A mortalidade por asma em crianças é baixa e mantém a tendência de queda no período estudado em todas as faixas etárias pediátricas

Doença respiratória em menores de 5 anos no sul do Brasil: influência do ambiente doméstico Respiratory illnesses in children younger than 5 years of age in southern Brazil: the influence of the home environment

OBJETIVO: Estabelecer a prevalência de doenças agudas do trato respiratório inferior e os fatores de risco relacionados às condições de moradia em crianças de 0 a 59 meses na Cidade do Rio Grande, Estado do Rio Grande do Sul, Brasil. MÉTODOS: Foi realizado um estudo transversal de base populacional com 775 crianças. Foram aplicados questionários padronizados às mães ou responsáveis pelas crianças, em seus domicílios, e coletadas informações sobre condições de habitação, nível socioeconômico e tabagismo. Também foram investigados: o estado nutricional, a duração da amamentação, o atendimento pré-natal e a utilização dos serviços de saúde. As variáveis ambientais foram analisadas individualmente e em conjunto, em um escore ambiental que englobou 10 variáveis - tipo de construção, tipo de piso, aquecimento doméstico, tipo de fogão, cão no quarto da criança, cão dentro de casa, gato no quarto da criança, gato dentro de casa, aglomeração e fumo materno - variando de 0 (melhor) a 10 (pior). A análise incluiu duas etapas: bivariada, com o cálculo da razão de prevalências de cada um dos fatores de risco, e multivariada, através de regressão logística. RESULTADOS: A prevalência geral de doença respiratória aguda baixa foi de 23,9%. Os principais fatores de risco identificados foram: escore ambiental > 3 pontos, menos de 5 anos de escolaridade materna, renda familiar mensal menor do que US$200,00, quatro ou mais pessoas dividindo o quarto da criança e tabagismo materno. A idade materna > 30 anos foi identificada como fator de proteção. CONCLUSÕES: É preciso implementar programas específicos de controle para as doenças respiratórias agudas na população estudada. O escore ambiental desenvolvido pode substituir as variáveis ambientais testadas, devendo ser aplicado em outros contextos para determinar a sua validade externa.<br>OBJECTIVE: To determine the prevalence of acute lower respiratory tract infections and the risk factors associated with living conditions among children up to 5 years of age in the city of Rio Grande, in the state of Rio Grande do Sul, Brazil. METHODS: A population-based cross-sectional study was carried out with 775 children. A standardized questionnaire was administered to the mother or other caregiver at the child's home in order to collect information on housing conditions, socioeconomic status, and smoking in the home. Additional variables examined included nutritional status, duration of breast-feeding, prenatal care, and utilization of health care services. Environmental variables were analyzed individually and were also grouped together in an "environmental score" that encompassed 10 variables: type of house construction, type of floor, home heating system, type of stove, dog in the child's room, dog in the house, cat in the child's room, cat in the house, number of people per room, and maternal smoking. The grouped environmental score ranged from 0 (best) to 10 (worst). The analysis included two stages: a bivariate stage, in which the prevalence ratio was calculated for each risk factor, and a multivariate stage, with logistic regression. RESULTS: The overall prevalence of acute lower respiratory tract infections was 23.9$ 200, four or more people sharing the child's bedroom, and maternal smoking. Maternal age > 30 years was found to protect against the development of respiratory illness. CONCLUSION: Specific programs need to be implemented to control acute respiratory illnesses in the population studied. In future studies with this population, the environmental score that we developed could be used in place of the complete set of environmental variables that we tested. This environmental score should be applied in other contexts so as to determine its external validity