Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers*

Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5–47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.     

Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension

The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned.     

Nebulized albuterol in acute childhood asthma: comparison of two doses

Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study. The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1). Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group. Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups. The high-dose therapy resulted in much higher serum albuterol levels than the standard dose. There was no correlation between the drug levels and side effects or initial and subsequent FEV1. It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses.     

Intramuscular salbutamol in treatment of acute exacerbations of childhood asthma.

Salbutamol was given by the intramuscular route to children aged 3 to 16 years with an attack of asthma. Results with a dose of 8 microgram/kg were favourable but suggested that a higher dose might be more so. 16 children thereafter were treated with 20 microgram/kg which produced a greater mean increase in peak expiratory flow rates (PEFR) without increase in side effects. This dose was then used in a double-blind crossover trial of salbutamol against a saline placebo. Half of 36 children treated with 20 microgram/kg showed rapid clinical improvement, the maximum rise in PEFR occurring within the first 5 minutes. A rise in pulse rate and occasionally a tremor were the only side effects noted. We conclude that intramuscular salbutamol 20 microgram/kg is a safe and useful initial medication in the management of the asthmatic child suffering an acute exacerbation.     

The effect of nebulized budesonide treatment in children with mild to moderate exacerbations of asthma

Background: The role of inhaled corticosteroids in the treatment of acute asthma remains a controversial subject. Objective and methods: A randomized, double-blind, placebo-controlled parallel-group clinical trial on the effect of a 5-d course of nebulized budesonide treatment in children with mild to moderate exacerbation of asthma was performed. The need for systemic corticosteroid intervention was evaluated as the primary outcome measure. Results: Sixty-seven children aged 6 to 15 y were enrolled. During the emergency department phase, they received three nebulizations of either budesonide(1 mg/dose) or placebo, and then in the home phase of the study, they continued their study medications twice a day for another 4 d. Though the level of improvement in the emergency department phase was similar between the groups given either budesonide or placebo treatments (6.8±1.9% vs 4.0±1.5%, p=0.30, respectively), nebulized budesonide caused a trend towards a benefit in terms of the need for systemic corticosteroid intervention (2/33 vs 7/34, p=0.07), but not in secondary outcome measures.

Conclusion: Though we show a tendency towards a benefit with nebulized budesonide in children with mild to moderate exacerbations in terms of prevention of progression of the illness, the documented benefit is small and includes, at least, consideration for clinical significance, cost-effectiveness, impracticality and safety.     

Cardiotoxicity during treatment of severe childhood asthma

We prospectively evaluated 20 patient admissions for severe exacerbation of childhood asthma at The Children's Hospital, Boston, to detect evidence of cardiotoxicity. Evidence of cardiotoxicity was found in all six patient admissions for which isoproterenol infusion was utilized. This included marked elevation of serum creatine phosphokinase isoenzyme (CPK-MB) levels and electrocardiogram abnormalities consistent with transient myocardial ischemia. Peak serum CPK-MB levels were significantly lower and electrocardiogram abnormalities were significantly less frequent during 14 patient admissions for which isoproterenol infusion was not utilized. Risk factors associated with cardiotoxicity included tachycardia, hypercapnia, acidosis, and intravenous isoproterenol therapy. We conclude that cardiotoxicity is not infrequent during therapy for severe exacerbations of childhood asthma. Electrocardiograms and measurement of serum CPK-MB levels are sensitive, useful, and readily obtained indicators of cardiotoxicity. Abnormalities of these studies may detect cardiotoxicity prior to the occurrence of more blatant or catastrophic manifestations of cardiotoxicity. We therefore recommend serial monitoring of serum CPK-MB levels and electrocardiograms for all children requiring an admission to the intensive care unit for management of severe asthmatic exacerbation.     

Childhood obesity increases duration of therapy during severe asthma exacerbations.

OBJECTIVES: Childhood obesity contributes to a wide array of medical conditions, including asthma. There is also increasing evidence in adult patients admitted to the intensive care unit (ICU) that obesity contributes to increased morbidity and to a prolonged length of stay. We hypothesized that obesity is associated with the need for increased duration of therapy in children admitted to the ICU with status asthmaticus. DESIGN: Retrospective cohort study. SETTING: A tertiary pediatric ICU in a university-affiliated children's hospital. PATIENTS: We retrospectively examined data from all children older than 2 yrs admitted to the ICU with status asthmaticus between April 1997 and June 2004. Children were classified as normal weight (<95% weight-for-age percentile) or obese (>95% weight-for-age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 209 children admitted to the ICU with asthma, 45 (22%) were obese. Compared with children of normal weight, the obese children were older (9.7 +/- 4.4 vs. 8.0 +/- 4.3 yrs, p = .02), more likely to be female (60% vs. 37%, p < .01), and more likely to have been admitted to the ICU previously (40% vs. 20%, p = .01). The obese children also had a statistically significant difference in race (more likely to be Hispanic) and in baseline asthma classification (more likely to have persistent asthma). Despite similar severity of illness at ICU admission, obese children had a significantly longer ICU length of stay (116 +/- 125 hrs vs. 69 +/- 57 hrs, p = .02) and hospital length of stay (9.8 +/- 7.0 vs. 6.5 +/- 3.4 days, p < .01). Obese children also received longer courses of supplemental oxygen, continuous albuterol, and intravenous steroids. CONCLUSIONS: Childhood obesity significantly affects the health of children with asthma. Obese children with status asthmaticus recovered more slowly from an acute exacerbation, even after adjustment for baseline asthma severity and admission severity of illness.     

Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone early in the emergency room management of acute asthma, we conducted a double-blind, placebo-controlled trial. Eighty children, 2 years to 12 years of age, with acute moderate attacks of asthma, were randomized into two groups. One group received nebulized salbutamol (0.15 mg/kg) and placebo at half-hourly intervals for three doses, and a single dose of oral prednisolone (2 mg/kg) (prednisolone group) and other group received three doses of nebulized salbutamol and budesonide (800 microg) at half-hourly intervals and a single dose of placebo tablets (budesonide group). The baseline characteristics of the two groups were similar, but after three doses of nebulization oxygen saturation, respiratory rate, pulmonary index and respiratory distress score were significantly improved in the budesonide group compared to prednisolone group (p < 0.01). The proportion of patients who were fit for discharge at the end of 2 h after the third dose of nebulization was significantly higher in the budesonide group than in the prednisolone group (22/ 41, 54% vs 7/39, 18%, p < 0.001). The data suggest that a combination of nebulized salbutamol and budesonide should be preferred in the emergency room management of children with acute moderate to severe exacerbation of asthma and who are not on prior oral or inhaled steroid therapy.     

Long term atropine in chronic severe childhood asthma

: The efficacy of adding oral or inhaled atropine sulphate to the maintenance therapy of 12 children with severe chronic asthma was assessed using a double blind crossover study lasting three months. There was no obvious subjective or objective clinical difference between either form of atropine sulphate and placebo. Twice daily peak flow rates were not significantly different for the three treatment periods. However, during oral atropine therapy there was a significant improvement in FEV₁/ VC (P < 0.05) and in RV/TLC (P< 0.05) compared to placebo. Inhaled atropine had no significant effect on baseline pulmonary function testing. No side effects were encountered. Further clinical trials are necessary to confirm the beneficial effect of long term oral atropine sulphate in the treatment of children with severe chronic asthma.     

Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children

OBJECTIVES: Oral budesonide has been found to be efficacious for mild to moderate Crohn's disease in adults, with equal improvement rates for budesonide and prednisone. We report the results of a retrospective study of budesonide treatment in mild to moderate Crohn's disease in children. STUDY DESIGN: Charts of patients treated with budesonide (n = 62) with a pediatric Crohn's Disease Activity Index of 12.5 to 40 were compared with a cohort of 58 age-matched patients treated with prednisone. RESULTS: Among children treated with budesonide, 48% had remission compared with 77% of the children treated with prednisone (P =.001). Among patients who had failed previous medical therapy with mesalamine, 59% had remission with budesonide (9 mg/day). Remission with prednisone occurred in 73% of children who failed to achieve remission with budesonide. Patients responding to budesonide had significantly milder disease compared with nonresponders who had remission while taking prednisone. CONCLUSIONS: Budesonide is useful in mild to moderate Crohn's disease in children. It is more effective than mesalamine and antibiotics but less effective than prednisone. Budesonide should be considered for first-line therapy in mild to moderate Crohn's disease.     

A comparison of oral dexamethasone with oral prednisone in pediatric asthma exacerbations treated in the emergency department

The aim of this study was to determine if 2 doses of oral dexamethasone are as effective as a 5-day course of oral prednisone in preventing relapse for pediatric asthma exacerbations. Patients presenting to the emergency department with an asthma exacerbation were randomized to receive 0.6 mg/kg of dexamethasone or 2 mg/kg of prednisone in a prospective, double-blind study. The primary outcome was relapse within 10 days, and the secondary outcome was vomiting in the emergency department. Eighty-nine patients completed the study: 38 in the prednisone group and 51 in the dexamethasone group. In all, 3 patients in the prednisone group (8%) and 8 patients in the dexamethasone group (16%) required an unscheduled follow-up visit (P = .27). In all, 7 patients in the prednisone group (18%) and 5 patients in the dexamethasone group (10%) had vomiting ( P = .24). No difference was found in the relapse rate or incidence of vomiting between patients given prednisone and dexamethasone for pediatric asthma exacerbations.     

雾化吸入布地奈德治疗婴幼儿哮喘急性发作的多中心临床观察

目的 观察不同起始剂量布地奈德混悬液雾化吸入(budesonide inhalation,BI)治疗婴幼儿中重度哮喘急性发作的疗效和安全性.方法 2008年9月至2010年4月,上海交通大学附属第一人民医院儿内科、上海交通大学医学院附属新华医院儿内科及复旦大学附属儿科医院呼吸科共收集6个月～3岁的中重度哮喘急性发作的住院患儿150例,随机分为高起始剂量BI组和常规起始剂量BI组.高起始剂量BI组给予雾化吸入BI 1 mg/次,每8小时1次,连用2d.常规起始剂量BI组给予雾化吸入BI 0.5 mg/次,每8小时1次,连用4 d.两组均按需给予博利康尼雾化吸入2.5 mg/次.主要疗效指标为入院时(0 h)及入院后8、16、24、48、72 h的临床症状评分;次要疗效指标为β2受体激动剂、全身糖皮质激素使用情况、住院总天数及医疗费用.结果采用 SPSS 13.0统计软件进行分析.结果 (1)两组组内治疗后各时间点的临床症状评分与入院时比较均明显降低,差异有统计学意义(P＜0.05);高起始剂量BI组较常规起始剂量B1组在治疗后8h、16h能更快地改善症状,提高临床症状评分(2.87±1.60 vs4.48 ±2.24,2.48±1.56 vs 3.25±1.82)(P＜0.01).(2)高起始剂量BI组特布他林的使用量、全身激素的累积使用量均明显减少[(16.27±12.99) mg vs (22.90±18.27) mg,(4.54±18.18) mg vs (11.16±21.34) mg](P＜0.05);而平均住院天数、住院总费用两组比较差异无统计学意义(P＞0.05).(3)全部受试对象未见鹅口疮、声音嘶哑等与吸入激素相关的不良反应.结论 对于中重度哮喘急性发作的婴幼儿,高起始剂量BI治疗能更快地控制症状,减少全身激素的使用量,具备较好的安全性,值得临床推广.     

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目的研究布地奈德雾化液(BIS)吸入治疗儿童咳嗽变异性哮喘(CVA)的疗效。方法 2008-04-04—2009-03-22期间,采用开放性、多中心非干预性调研,在全国39个中心入选了903例5岁及5岁以下CVA患儿。雾化吸入(BIS)1～2mg/d,共7周。研究期间共有5次访视,评估雾化吸入BIS治疗后CVA患儿症状评分改变、缓解药物的使用、依从性和疾病控制情况等。结果 7周的观察期间,患儿总退出率8.97%(81/903)。雾化吸入BIS治疗后患儿的症状总评分(第1周4.0分vs第7周0.5分),白天症状评分(第1周2.4分vs第7周0.3分),夜间症状评分(第1周1.5分vs第7周0.2分)均明显下降(P均<0.0001)。使用支气管舒张剂的患儿比例明显降低(第1周39.42%vs第7周2.99%,P<0.0001),使用支气管舒张剂的中位数从第1周的5.8d/周减少到治疗终点时的3.9d/周。第7周时仍有87.49%的患儿依从性良好。依从性良好的患儿达到有效控制的可能性是依从性较差患儿的2.698倍,而且CVA复发可能性较低(OR=0.439)。没有自发不良事件报告。结论 BIS雾化吸入治疗能改善CVA患儿的症状评分,减少支气管舒张剂的应用,患儿依从性和安全性良好。     

Inhaled budesonide in acute asthma

OBJECTIVE: To evaluate the efficacy of aerosolized budesonide therapy (with metered dose inhaler and spacer) early in the emergency room treatment of acute moderate exacerbations of bronchial asthma in children. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Paediatric Emergency Service of an urban teaching hospital and a tertiary case referral centre. STUDY POPULATION: Sixty children between 3 and 12 years of age with an acute moderate exacerbation of asthma. INTERVENTION: All patients received humidified oxygen (5-8 L/min by Venturi(R) mask; Hudson Respiratory Care, Temecula, CA, USA), nebulized salbutamol (0.15 mg/kg in 3 mL saline) and were randomized to receive either budesonide (400 microg) or placebo inhalation (MDI and spacer) at half hourly intervals for three doses. If there was an inadequate response or no response to treatment at the end of 2 h, oxygen and salbutamol therapy were continued and the patient was given one of dose intravenous hydrocortisone and was started on an aminophylline infusion. If there was no response at the end of a further 4 h, the patient was hospitalized. INITIAL EVALUATION AND MONITORING: Colour, respiratory rate (RR), heart rate, accessory muscle usage, chest retraction, wheeze, oxygen saturation (by pulse oximetery) and peak expiratory flow rate (PEFR) was recorded at admission and thereafter at hourly intervals for 3 h or until till the child recovered. The need for oxygen therapy after 2 h and need for hospitalization were recorded. MAIN RESULTS: Both groups showed a significant improvement in respiratory status at the end of 2 h. However, children in the intervention group showed greater improvements in RR and PEFR (P < 0. 05) and respiratory distress score (P < 0.1). A significantly lower proportion of the intervention group patients required oxygen therapy for more than 2 h (23% vs 50%; P < 0.05) and aminophylline infusion and systemic corticosteroid therapy (7% vs 27%; P < 0.05). None of the children in the budesonide group, in contrast to 23% of those in the placebo group, required hospitalization (P < 0.05). The length of hospital stay (i.e. time taken to recover from acute asthma) was significantly shorter in the intervention group (3.2 +/- 2.5 h) than in the placebo group (7.8 +/- 11.3 h; P < 0.01). CONCLUSION: Aerosolized budesonide therapy (with MDI and spacer) together with nebulized salbutamol early in the emergency room treatment of acute moderate exacerbations of asthma helped in early recovery and decreased the need for hospitalization. It may be worthwhile calculating this regimen for home-based early treatment of acute exacerbations.