Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.

We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.     

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide.

AIMS: To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler). DESIGN: A randomised double blind, placebo controlled crossover study with two six-week periods. SETTING: Outpatient clinic in secondary referral centre. SUBJECTS: A total of 27 prepubertal children aged 6-13 years. INTERVENTIONS: Formoterol 12 microg and dry powder budesonide 100 microg twice daily in one period; placebo and dry powder budesonide 200 microg twice daily in the other. OUTCOME MEASURES: Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control. RESULTS: During budesonide 200 microg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods. CONCLUSIONS: In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study

OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.     

Fluticasone propionate in asthma: a long term dose comparison study.

BACKGROUND: Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma. AIMS: To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year. METHODS: One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured. RESULTS: There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose. CONCLUSION: This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.     

Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers

The aim of this study was to investigate whether budesonide, for 10 d, administered at the first sign of an upper respiratory tract infection, could reduce asthma symptoms in 1-3-y-old children with asthma during infections. The primary efficacy variable was symptom scores. The study had a multicentre, randomized, double-blind, placebo-controlled design with parallel groups. Fifty-five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask. Each child was monitored for 1 y. Budesonide was given 400 microg q.i.d. for the first 3 d and b.i.d. for 7 d. Symptoms (cough, wheeze, noisy breathing and breathlessness) were scored (0-3) daily by the parents. Asthma symptom scores were lower in children treated with budesonide than in those given placebo. The effect was most pronounced for cough and noisy breathing, but it did not affect the need for hospital care. In conclusion, treatment with budesonide, started at the first sign of a respiratory infection, reduced asthma symptoms in toddlers with episodic asthma.     

Effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home

Many clinicians advise their patients to increase the dose of inhaled corticosteroids during acute asthma exacerbations, without strong clinical evidence supporting this treatment. This study investigates the effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. The study population consisted of children with mild intermittent, mild and moderate persistent asthma aged 1 to 14 years who were treated in our outpatient clinic with inhaled budesonide for 1 year. After participating in an asthma education session, the parents were instructed to initiate treatment with inhaled budesonide at the first signs of asthma exacerbation, starting with 200 to 400 microg budesonide, in combination with beta-2 agonists 4 times a day and followed by a decrease in the dose in 4 to 8 days. Asthma status and peak expiratory flow rates were measured in the 3 monthly follow-up visits. Only children who complied with the treatment regimen and came for follow-up visits regularly were included in the final analysis. One hundred fifty children used our treatment protocol with inhaled budesonide to control their asthma attacks. Clinical improvement of asthma symptoms was achieved after a mean of 1.8 +/- 0.7 days from the beginning of treatment. The parents were able to control 94% of the 1,061 episodes of asthma exacerbation occurring during a cumulative follow-up period of 239 years. In the 3-month period before enrollment, 101 children (67%) had used oral corticosteroids to control their asthma attacks and 50 (33%) were hospitalized. During the entire follow-up period, only 11 children (7%) used oral corticosteroids, and none of the children were hospitalized. The present study demonstrates that children with asthma can control their exacerbations at home using inhaled corticosteroids (budesonide). Treatment, starting with relatively high doses followed by a rapid reduction in dose over 4-8 days, resulted in a decrease in the use of oral steroids and in hospitalization. To achieve good results, patient compliance is essential.     

Montelukast vs. inhaled low-dose budesonide as monotherapy in the treatment of mild persistent asthma: a randomized double blind controlled trial

BACKGROUND: Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Aim: To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1). METHODS: Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study. RESULTS: Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents. CONCLUSION: Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.     

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.     

Systemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma

Forty children aged 1-3 y completed a placebo-controlled study on the effects of 10 d of inhaled budesonide for asthma caused by respiratory tract infection. The effects on symptoms were significantly better in the active than in the placebo group. In 20 of these children the systemic effects of high-dose inhaled budesonide for 10 d and the effect of a 3-d course of oral betamethasone on asthma exacerbation were evaluated. Systemic effects were evaluated by measuring morning cortisol in serum and urine, and the bone markers osteocalcin, ICTP (the C-terminal telopeptide region of type I collagen) and PIIINP (an N-terminal propeptide of type III procollagen) in serum before and at the end (d 7-10) of treatment (1600 microg budesonide d(-1) for 3 d and 800 microg for 7 d). In 9 children, measurements were taken on d 3 of a 3-d course of betamethasone (6, 4 and 2 mg) for asthma exacerbation and 14 d later. There were no signs of systemic effects after 7-10 d of budesonide. After 3 d of betamethasone, serum cortisol decreased from a median of 263 to 26 nmol l(-1), urine cortisol/creatinine from 19.9 to 7.2 nmol l(-1), osteocalcin from 31.4 to 5.5 microg l(-1), ICTP from 19.4 to 8.5 microg l(-1) and PIIINP from 12.3 to 5.9 microg l(-1). Two weeks later, the levels were back to normal. In conclusion, short courses of oral betamethasone have pronounced systemic effects, whereas 10 d of high doses of budesonide do not produce significant systemic effects.     

Nebulized budesonide after hospitalization for recurrent bronchial obstruction in children younger than 18 months

A multi‐center, double‐blind, randomized dose–response study was performed to assess the effect of 3 months of treatment with two different doses of inhaled nebulized budesonide in children with acute recurrent bronchial obstruction (BO) causing hospitalization. Steroid‐naive children younger than 18 months were included when admitted to hospital because of BO for at least the second time, and were followed‐up monthly for 15 months. Forty‐five of 49 subjects (43 boys, 2 girls) (mean age 9.3 months upon inclusion) completed the study. Twenty‐four patients (20 boys, 4 girls) received nebulized budesonide 0.5 mg twice daily for 1 month followed by 0.25 mg daily for the next 2 months, whereas 25 children received 0.1 mg twice daily throughout the 3‐month treatment period. Outcome (number of BO episodes, time to first BO after start of treatment, and use of rescue medication), as well as height/length and weight, were assessed at the start of treatment and monthly for the following 3 months, as well as for 12 months after cessation of treatment (15 months in total). There was an overall tendency towards better symptom control (fewer episodes of acute BO during treatment and follow‐up, fewer hospital visits because of acute BO, lower clinical score during follow‐up, and less use of rescue medication during follow‐up) in the high‐dose treatment group vs. the low‐dose treatment group. However, the differences did not reach statistical significance for any of the outcomes. The only significant difference in effect between the groups was fewer children in the high‐dose group treated openly with nebulized budesonide during follow‐up. Length/height and weight gain did not differ significantly between the two treatment groups throughout the study. There was no significant dose‐dependent beneficial effect of 3 months of treatment with nebulized budesonide in infants and toddlers with at least two hospitalizations for acute bronchial obstruction.     

达良好控制哮喘患儿停用低剂量吸入性糖皮质激素的临床随访研究

目的 通过随访达良好控制哮喘患儿停用低剂量吸入性糖皮质激素（ICS）后哮喘急性发作情况,以及实验室指标的动态变化,以期为哮喘患儿的长期控制最佳方案提供依据。方法 根据家长意愿,将63例达到良好控制的哮喘患儿分为ICS治疗组（n=35）和停药组（n=28）,进行18个月随访,每3个月进行评估,观察哮喘急性发作情况,并动态监测两组患儿肺功能和呼出气一氧化氮（FeNO）浓度,以及儿童哮喘控制测试（C-ACT）评分等指标进行分析。结果 随访第3、6、9、12个月时,FeNO在两组间比较差异无统计学意义（P > 0.05）;但在随访第15、18个月时,停药组FeNO显著高于治疗组（P < 0.05）。6次随访时点内C-ACT在两组间比较差异无统计学意义（P > 0.05）。随访第3、6、9、12个月时,第1秒用力呼气容积占预计值的百分比（FEV1%）、第1秒用力呼气量占用力肺活量比值（FEV1/FVC%）、最大呼气中期流速占预计值百分比（MMEF%）、最大呼气50%肺活量的瞬间流速（MEF50%）等指标在两组间比较差异无统计学意义（P > 0.05）;但在随访第15、18个月时,治疗组MMEF%、MEF50%显著高于停药组（P < 0.05）。治疗组随访期间有3例（9%）患儿哮喘发作,停药组有8例（29%）患儿哮喘发作,停药组哮喘复发率高于治疗组（P=0.0495）。结论 持续吸入低剂量ICS可维持哮喘患儿肺功能稳定,减少哮喘发作。     

间歇与每日吸入布地奈德对轻度持续性哮喘儿童肺功能及呼出气一氧化氮的影响

目的 探讨间歇与每日吸入布地奈德对轻度持续性哮喘儿童的肺功能及呼出气一氧化氮（FeNO）的影响。方法 选择2016年1月至2018年1月就诊的6~14岁轻度持续性哮喘儿童共120例,采用分层随机法分为间歇吸入组60例（出现哮喘征兆时吸入布地奈德200?μg/d,持续6周）和每日吸入组60例（持续吸入布地奈德200?μg/d）。于治疗第3、6、9、12月进行随访,比较两组患儿基线资料、FeNO及肺功能指标的变化、激素用量、哮喘发作次数及哮喘病情控制情况。结果 两组患儿在治疗起始时,基线资料及FeNO、肺功能指标比较差异均无统计学意义（P > 0.05）。随着治疗时间的延长,两组患儿FeNO逐渐降低,肺功能指标逐渐改善（P < 0.001）。与间歇吸入组比较,每日吸入组在降低FeNO和提高1秒呼气量占预计值百分比（FEV1% pred）上具有优势（P < 0.001）。吸入方式和治疗时间对FeNO及肺功能指标的影响具有交互作用（P < 0.001）,每日吸入组在治疗3个月后FeNO及肺功能指标迅速改善并趋于平稳,而间歇吸入组6个月后趋于平稳。治疗12个月后,两组患儿身高、体重增长及病情控制程度比较差异均无统计学意义（P > 0.05）,间歇吸入组患儿布地奈德吸入量要明显少于每日吸入组（P < 0.05）,但哮喘发作次数要多于每日吸入组（P < 0.05）。结论 间歇和每日吸入布地奈德对轻度持续性哮喘儿童能够达到相同的哮喘控制水平,且对患儿身高、体重增长均无影响;每日吸入布地奈德能够更加快速有效地降低FeNO和提高FEV1% pred;虽然间歇吸入能够减少激素用量,但有更高的哮喘发作风险。     

Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma

The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV₁) and symptoms) were measured 24 h after treatment initiation. FEV₁ improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.     

Increased glycosaminoglycans in the urine of asthmatic children on inhaled corticosteroids

Increased extracellular matrix (ECM) deposition in the airway wall contributes to the airway remodeling in asthmatics. Glycosaminoglycans (GAGs) are polysaccharides attached to a protein core in order to form proteoglycans, a component of the ECM. In this study, we investigated the possible influence of long-term treatment with inhaled corticosteroids (ICS) on urinary GAGs levels of asthmatic children. Seventy asthmatic children (41 boys), aged 6.8-12.5 yr, participated in the study. About 44 were treated with inhaled budesonide via turbuhaler for 2-35 months (median 12 months) and 26 were on relief medications. About 30 healthy controls were also studied. GAGs were precipitated from early morning urine samples, collected, isolated and quantified using uronic acid-carbazole reaction and expressed as uronic acid (UA) in microg/g/Cr(u)/m2. Urinary GAGs values did not differ significantly between controls and asthmatics but significant differences were found between children on ICS and asthmatics on relief medications (p < 0.001). There was a positive correlation between the daily dose of inhaled budesonide and the urinary GAGs values (r = 0.32, p = 0.037) whereas a threshold distinguishing 'low' vs. 'high' doses of ICS was found to be at 300 microg/m2 per day with a significant difference in urinary GAGs secretion (p = 0.006). Our data show that urinary GAGs secretion is reduced in asthmatic children that used only relief medication but it is increased in those on long-term treatment with ICS. A dose dependent effect of ICS was also detected.     

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.     

Addition of antileukotriene agents to inhaled corticosteroids in children with persistent asthma

BackgroundIn the treatment of children with mild persistent asthma, low-dose ICS are recommended as the preferred monotherapy (referred to as step 2 of therapy). In children with inadequate asthma control on low doses of ICS (step 2), asthma management guidelines recommend adding an LTRA to existing ICS as one of three therapeutic options to intensify therapy (step 3).MethodsSearch strategy: Trials were identified from the Cochrane Airways Group Specialised Register of Trials, which is derived from systematic searches of bibliographical databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, AMED and CINAHL, and a manual search of respiratory journals and meeting abstracts, as well as the web-site www.clinicaltrials.gov. The search was conducted until January 2013.Selection criteria: Randomized controlled trials (RCTs) that involved children and adolescents one to 18 years of age, with asthma, who remained symptomatic despite the use of a stable maintenance dose of ICS, and in whom LTRAs were added to ICS and compared with the same, an increased or a tapering dose of ICS for at least four weeks were considered for inclusion.ResultsFive paediatric (parallel group or cross-over) trials met the inclusion criteria. Two (40%) trials were considered to be at a low risk for bias. Four published trials, representing 559 children (≥6 years of age) and adolescents with mild-to-moderate asthma, contributed data to the review. No trial enrolled preschool-age children. All trials used montelukast as the LTRA, administered for between four and 16 weeks. Three trials evaluated the combination of LTRAs and ICS compared with the same dose of ICS alone (step 3 versus step 2). No statistically significant group difference was observed in the only trial reporting participants with exacerbations requiring oral corticosteroids over four weeks (n=268 participants; RR 0.80 [95% CI 0.34 to 1.91]). There was also no statistically significant difference in percent change in forced expiratory volume in 1 s (FEV₁) in this trial, with a mean difference (MD) of 1.3 (95% CI −0.09 to 2.69); however, a significant group difference was observed in the morning and evening peak expiratory flow rates: n=218 participants; MD 9.70 L/min (95% CI 1.27 L/min to 18.13 L/min) and MD 10.70 L/min (95% CI 2.41 L/min to 18.99 L/min), respectively. One trial compared the combination of LTRAs and ICS with a higher dose of ICS (step 3 versus step 3). No significant group difference was observed in this trial for participants with exacerbations requiring rescue oral corticosteroids over a 16-week period (n=182 participants; RR 0.82 [95% CI 0.54 to 1.25]), nor was there any significant difference in exacerbations requiring hospitalization. There was no statistically significant group difference in withdrawals overall or because of any cause with either protocol. No trial explored the impact of adding LTRAs as a means to taper the dose of ICS.ConclusionsThe addition of LTRAs to ICS is not associated with a statistically significant reduction in the need for rescue oral corticosteroids or hospital admission compared with the same or an increased dose of ICS in children and adolescents with mild to moderate asthma. Although LTRAs have been licensed for use in children for >10 years, the paucity of paediatric trials, the absence of data regarding preschool-age children and the variability in the reporting of relevant clinical outcomes considerably limit firm conclusions. At present, there is no firm evidence to support the efficacy and safety of LTRAs as add-on therapy to ICS as a step 3 option in the therapeutic arsenal for children with uncontrolled asthma symptoms on low-dose ICS.The full text of the Cochrane Review is available in The Cochrane Library (1).     

Inhaled corticosteroids during and after respiratory syncytial virus-bronchiolitis may decrease subsequent asthma

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper-reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 µg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 µg twice per day for two months. Follow-up consisted of out-patient check-ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.     

Low‐dose budesonide improves exercise‐induced bronchospasm in schoolchildren

The aim of this study was to compare the clinical efficacy of low‐dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler^®, on exercise‐induced bronchoconstriction (EIB) in children with mild asthma. Fifty‐seven steroid‐naive children (7–16 years old; 41 boys, 16 girls) with EIB participated in this sub‐population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s ( FEV ₁) ≥ 10% after a standardized treadmill test. Mean baseline FEV ₁ was 100.3% of predicted, and mean maximum fall in FEV ₁ after the standardized exercise test was 22%. The study was a double‐blind, randomized, parallel‐group design. After 2 weeks of run‐in, the children received inhaled budesonide 100 µg or 200 µg once daily in the morning, 100 µg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV ₁ after the exercise test was significantly less in all three budesonide groups (7.2–7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p < 0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.