RESUMO
BACKGROUND: Most international asthma guidelines recommend that children ≤5 years with asthma or recurrent wheezing be treated with daily low- moderate dose inhaled corticosteroids (ICS) as the preferred controller and leukotriene receptor antagonists (LTRA) as alternative therapy. There is no systematic review comparing the efficacy of ICS versus LTRA monotherapy in this age group. OBJECTIVE: To compare the efficacy of daily ICS versus LTRA in preschoolers with asthma or recurrent wheezing. METHODS: Randomized, prospective, controlled trials published by December 2017, with a minimum of 3-month therapy with daily ICS versus LTRA were identified. The co-primary outcomes were the number of wheezing episodes and daily symptom score. Secondary outcomes included unscheduled emergency visits, need of rescue systemic corticosteroids (SC), hospitalization for exacerbations, lung function, and adverse effects. RESULTS: Of 29 trials identified, six studies (n = 3204 patients, 62% males, age range: 6-54 months) met the inclusion criteria; two were at low risk of bias. Five pertained to children with asthma; one to those with recurrent wheezing. No outcomes were similarly reported in the six studies, preventing meta-analysis. Based on trials at lowest risk of bias and the largest open-labelled studies, ICS was associated with better control of symptoms and less exacerbations than LTRA. And also less need for rescue SC. Insufficient data of high quality prevented firm conclusions on other secondary outcomes. CONCLUSIONS: In preschoolers with asthma or recurrent wheezing, daily ICS appears more effective than daily LTRA for improving symptom control and decreasing exacerbations, particularly those requiring rescue SC, although the magnitude of benefit remains to be quantified.
Assuntos
Acetatos/uso terapêutico , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Quinolinas/uso terapêutico , Sons Respiratórios/efeitos dos fármacos , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/fisiopatologia , Pré-Escolar , Ciclopropanos , Quimioterapia Combinada , Hospitalização , Humanos , Lactente , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/efeitos adversos , Estudos Prospectivos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Recidiva , SulfetosRESUMO
In the present review, we focus on evidence-based data for the use of inhaled corticosteroids (ICS), leukotriene receptor antagonist (LTRA), long-acting beta2-agonits (LABA) and oral corticosteroids (OCS), with a special emphasis on well-performed randomized clinical trials (RCTs) and meta-analyses of such trials for the chronic management of asthma/wheeze in infants and preschoolers. RESULTS: Seven meta-analyses and 14 RCTs were reviewed. Daily ICS should be the preferred drug for infants/preschoolers with recurrent wheezing, especially in asthmatics. For those with moderate or severe episodes of EVW, the use of high intermittent ICS doses significantly reduce the use of OCS. There is no evidence of effect of intermittent ICS at low-moderate dose in preschoolers with mild EVW episodes. In preschoolers with asthma, there were no significant differences between daily vs. intermittent ICS in terms of asthma exacerbations with insufficient power to conclude to equivalence; however, for other asthma control outcomes, daily ICS works significantly better than intermittent ICS for older children. Daily ICS is superior to daily or intermittent LRTA for reducing symptoms, preventing exacerbations, and improving lung function. No RCTs testing combination therapy with ICS and LABA (or LTRA) were published in infant/preschoolers. Parent-initiation of OCS at the first sign of symptoms is not effective in children with recurrent wheezing episode. In terms of ICS safety, growth suppression is dose and molecule-dependent but it's effect is not cumulative beyond the first year of therapy and may be associated with some catch-up growth while on or off therapy. Linear growth must be monitored as individual susceptibility to ICS drugs may vary considerably.
RESUMO
BACKGROUND: Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth. OBJECTIVES: To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment). SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials (CAGR), 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 to look for potential relevant unpublished studies. The literature search was conducted in January 2014. SELECTION CRITERIA: Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child. MAIN RESULTS: We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%. Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period. Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi(2) = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 µg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated linear growth velocity in the fluticasone group at 12 months after treatment cessation, but there remained a statistically significant difference of 0.7 cm in height between the fluticasone and placebo groups at the end of the three-year trial. One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 µg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with those treated with placebo. AUTHORS' CONCLUSIONS: Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma. PLAIN LANGUAGE SUMMARY: Do inhaled corticosteroids reduce growth in children with persistent asthma? Review question: We reviewed the evidence on whether inhaled corticosteroids (ICS) could affect growth in children with persistent asthma, that is, a more severe asthma that requires regular use of medications for control of symptoms. BACKGROUND: Treatment guidelines for asthma recommend ICS as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, parents and physicians always remain concerned about the potential negative effect of ICS on growth. Search date: We searched trials published until January 2014. Study characteristics: We included in this review trials comparing daily use of corticosteroids, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma. KEY RESULTS: Twenty-five trials involving 8471 children with mild to moderate persistent asthma (5128 treated with ICS and 3343 treated with placebo or non-steroidal drugs) were included in this review. Eighty percent of these trials were conducted in more than two different centres and were called multi-centre studies; five were international multi-centre studies conducted in high-income and low-income countries across Africa, Asia-Pacifica, Europe and the Americas. Sixty-eight percent were financially supported by pharmaceutical companies. Meta-analysis (a statistical technique that combines the results of several studies and provides a high level of evidence) suggests that children treated daily with ICS may grow approximately half a centimeter per year less than those not treated with these medications during the first year of treatment. The magnitude of ICS-related growth reduction may depend on the type of drug. Growth reduction seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. Evidence provided by this review allows us to conclude that daily use of ICS can cause a small reduction in height in children up to 18 years of age with persistent asthma; this effect seems minor compared with the known benefit of these medications for asthma control. QUALITY OF EVIDENCE: Eleven of 25 trials did not report how they guaranteed that participants had an equal chance of receiving ICS or placebo or non-steroidal drugs. All but six trials did not report how researchers were kept unaware of the treatment assignment list. However, this methodological limitation may not significantly affect the quality of evidence because the results remained almost unchanged when we excluded these trials from the analysis.
RESUMO
OBJECTIVE: To determine the performance characteristics of the Preschool Respiratory Assessment Measure (PRAM) in preschool and school-aged children with acute asthma. STUDY DESIGN: In a prospective cohort study, we examined the validity, responsiveness, and reliability of the PRAM in children aged 2 to 17 years with acute asthma. The study involved more than 100 nurses and physicians who recorded the PRAM on triage, after initial bronchodilation, and at disposition. Predictive validity and responsiveness were examined using disposition as outcome. RESULTS: The PRAM was recorded in 81% (n = 782) of patients at triage. The PRAM at triage and after initial bronchodilation showed a strong association with admission (r = 0.4 and 0.5, respectively; P < .0001), thus supporting its ability to distinguish across severity levels. The responsiveness coefficient of 0.7 indicated good ability to identify change after bronchodilation. The PRAM showed good internal consistency (Cronbach alpha = 0.71) and inter-rater reliability (r = 0.78) for all patients and across all age groups. CONCLUSIONS: Good performance characteristics were observed in all age groups, making the PRAM an attractive score for assessing asthma severity and response to treatment.
Assuntos
Asma/classificação , Índice de Gravidade de Doença , Doença Aguda , Adolescente , Albuterol/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To obtain parental perspectives on changes in sleep, breathing, quality of life (QOL), and neurobehavioral measures after adenotonsillectomy. STUDY DESIGN: This retrospective cohort study comprised otherwise healthy children evaluated for obstructive sleep apnea syndrome (OSAS) from 1993 to 2001. We compared those children who underwent adenotonsillectomy with those children who did not. The parents of 473 children (292 boys) 2 years of age and older were sent questionnaires to evaluate QOL and clinical and behavioral changes. For 94 children 3 years of age and older, behavioral changes were evaluated using the Conners' Parent Rating Scale-Revised (CPRS-R) for three different periods: pre-operatively/pre-polysomnography, postoperatively/postpolysomnography, and recently. RESULTS: One hundred and sixty-six questionnaires were returned (35%), 138 of which were complete with written consent provided. Compared with parents of unoperated children, parents of children who had adenotonsillectomy were more likely to report improvements in sleep, breathing, and QOL but not improvements in concentration, school performance, and intellectual or developmental progress. Both short and long term, there were no significant effects of adenotonsillectomy on any of the CPRS-R behavior subscales. CONCLUSION: From a parental perspective, adenotonsillectomy frequently improves sleep, breathing, and QOL but does not often improve neurobehavioral outcomes.
Assuntos
Adenoidectomia , Transtornos do Comportamento Infantil/etiologia , Qualidade de Vida , Respiração , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Sono , Tonsilectomia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: In previously well infants hospitalized with acute viral bronchiolitis, the effectiveness of repeated nebulized therapy with epinephrine (EPI) was compared with treatment with albuterol (ALB) or saline placebo (PLAC). STUDY DESIGN: In this randomized, double-blind, parallel-group, controlled trial, infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team. The primary outcome was length of hospital stay (LOS). Secondary outcomes included the time from admission until the infant had normal hydration, oxygenation, and minimal respiratory distress. RESULTS: A total of 149 infants were randomized; 50 were allocated to receive racemic EPI, 51 were given ALB, and 48 received PLAC. Baseline characteristics and pre-enrollment symptoms, signs, and therapy were similar between groups. There were no group differences in the primary outcome measure, mean LOS (hours)(+/- SD): EPI = 59.8 (62), ALB = 61.4 (54), and PLAC = 63.3 (47); P =.95 by intent-to-treat analysis. Group differences were not statistically significant in any of the secondary outcomes. CONCLUSIONS: There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis. Based on these results, we do not recommend routine use of either nebulized EPI or ALB in this patient group.