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.     

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.     

Once-daily ciclesonide in children: efficacy and safety in asthma

OBJECTIVE: To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug (CIC40), 80 mug (CIC80), and 160 mug (CIC160) with placebo in children with persistent asthma of all severities. STUDY DESIGN: Overall, 1031 children age 4 to 11 years were randomized into 2 identical double-blinded, placebo-controlled, parallel group studies consisting of a run-in phase followed by 12 weeks of treatment. Both studies were designed to allow for a prespecified integrated analysis. The primary outcome variable was change in forced expiratory volume in 1 second (FEV(1)) percent predicted between baseline and study end; treatment comparisons were assessed using analysis of covariance. Additional endpoints included asthma symptom scores, daily albuterol use, and safety, including hypothalamic-pituitary-adrenal (HPA) axis function. RESULTS: Baseline characteristics were comparable; 59.4% of patients had moderate asthma, and 24.1% had severe asthma. All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1) percent predicted versus placebo (CIC40, 11.97; CIC80, 13.58, P <.05; CIC160, 14.17, P < .01). Significant improvements in asthma symptoms (P < .01) and reductions in albuterol use were reported. Ciclesonide was well tolerated with no effect on HPA axis function. CONCLUSIONS: In this integrated analysis, ciclesonide was effective and well tolerated in children with persistent asthma.     

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.     

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.     

Budesonide: safety and efficacy aspects of its long-term use in children

Fifty-two asthmatic children aged 4 to 13 years (mean 9. 6) were enrolled in this open 12-month study of budesonide, 200 meg bid, administered by tube-spacer inhaler (INHALETE® ASTRA DRACO). The aim of the study was to assess long-term safety, as well as efficacy, of budesonide in children whose asthma was not adequately controlled by their current therapy. Children attended the clinic every three months for assessment of lung function and height. In addition, an adrenal function test and routine clinical chemistry and haematology were performed. Parents completed diary cards once each week, recording the child's PEF, asthma symptoms, β₂-agonist consumption and other medication (no prophylactic drugs or other inhaled steroids were allowed and oral steroids were used for emergency treatment only). There were significant increases in all clinic lung function tests (baseline to last visit) and in diary card PEF (first 3 months vs last 3 months). These were accompanied by decreases in asthma symptoms and use of β₂-agonists or other medication. There was no indication that growth was affected by study treatment and basal adrenal function (basal cortisol) did not change significantly throughout the study. The adrenal response to Synacthen had actually increased significantly by the end of the study. No serious adverse events were associated with budesonide treatment. In conclusion, regular budesonide therapy was associated with a significant improvement in lung function and symptoms over one year. Budesonide was well-tolerated by the children and appeared to have no adverse influence on either growth or adrenal function.     

Computerised paediatric asthma quality of life questionnaires in routine care.

BACKGROUND: Asthma quality of life questionnaires are not readily incorporated into clinical care. We therefore computerised the Paediatric Asthma Quality of Life Questionnaire (standardised) (PAQLQ(S)) and the Paediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ), with a colour-coded printed graphical report. OBJECTIVES: To (a) assess the feasibility of the electronic questionnaires in clinical care and (b) compare the child's PAQLQ scores with the parent's score, physician's clinical score and spirometry. METHODS: Children with asthma were given a clinical severity score of 1-4 (increasing severity) and then completed the PAQLQ(S) electronically (scores 1-7 for increasing quality of life in emotional, symptoms and activity limitation domains) followed by spirometry and physician review. Parents completed the PACQLQ. Inclusion criteria required fluent Hebrew and reliable performance of spirometry. Children with additional chronic diseases were excluded. RESULTS: 147 children with asthma aged 7-17 years completed PAQLQs and 115 accompanying parents completed PACQLQs, taking 8.3 (4.3-15) and 4.4 (1.5-12.7) min, respectively (mean (range)). Graphical reports enabled physicians to address quality of life during even brief visits. Children's (PAQLQ) and parents' (PACQLQ) total scores correlated (r = 0.61, p<0.001), although the children's median emotional score of 6.3 was higher than their parents' 5.7 (p<0.001), whereas median activity limitation score was lower than their parents': 5.0 and 6.8, respectively (p<0.001). No correlation was found with physician's clinical score or spirometry. CONCLUSIONS: Electronic PAQLQs are easy to use, providing additional insight to spirometry and physician's assessment, in routine asthma care. Future studies must assess impact on asthma management.     

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。     

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目的探讨符合我国儿童哮喘控制评估的方法。方法 2006年11月至2007年11月,采用前瞻、多中心、双盲、前后对照试验方法,在厦门、南宁、海口、青岛、成都等5个城市入选有效患儿239例(共700例次),进行为期3个月的观察评估(初诊及随诊)。记录哮喘严重程度分级、肺功能1秒用力呼气容积占预计值百分比(FEV1%)、6岁以上患儿检测峰流速(PEF),针对4～12岁患儿采用中文版儿童哮喘控制测试(C-ACT)、对7～14岁患儿采用中文版儿科哮喘生命质量调查问卷(PAQLQ)。结果中文版C-ACT信度Cronbachα值为0.8546,哮喘严重程度与FEV1%、PEF、C-ACT得分之间差异有高度显著性(P均<0.01)。哮喘控制、部分控制、未控制与FEV1%、PEF之间差异具有高度显著性(P均<0.01),C-ACT得分均值分别为24.46、21.85和15.37。ROC曲线分析得出C-ACT≤19时,为未控制;≥23时为控制,20～22为部分控制。与PAQLQ多元回归分析亦呈高度正相关。结论中文版C-ACT有良好的信度效度,可用来判断哮喘是否得到控制。     

儿童哮喘控制水平的影响因素和评估指标分析

目的 分析儿童哮喘控制水平的影响因素,评价哮喘评估指标的实用性。方法 选取185例哮喘患儿,采用问卷及肺功能检测的方法,分析儿童哮喘控制水平及影响因素,以及评估指标与哮喘控制水平的相关性。结果 185例患儿中,完全控制的139例 （75.1%）,部分控制的36例 （19.5%）,未控制10例 （5.4%）。是否规范吸入糖皮质激素和嗜酸性粒细胞计数水平对哮喘控制的影响有统计学意义 （P < 0.05）。第1秒用力呼气容积占预计值的百分比 （FEV1%）、呼出气一氧化氮 （FeNO）以及儿童哮喘控制测试问卷 （C-ACT）、儿科哮喘生命质量调查问卷 （PAQLQ）得分等哮喘检测指标在控制组、部分控制组和未控制组之间的差异有统计学意义 （P < 0.05）。哮喘患儿FEV1%与C-ACT、PAQLQ呈正相关性 （r = 0.214、0.312,P < 0.05）,而与FeNO水平没有显著的相关性 （r = -0.18,P > 0.05）。结论 吸入糖皮质激素治疗的依从性和嗜酸性粒细胞计数水平是儿童哮喘控制的影响因素。联合FEV1%、FeNO水平以及C-ACT、PAQLQ评分等多个指标评估哮喘控制水平,更有利于儿童哮喘的临床诊疗。     

Asthma drug adherence in a long term clinical trial.

AIM: To measure drug adherence in children with mild asthma receiving long term prophylactic treatment. METHODS: Double blind randomised placebo controlled trial. Patients received inhaled budesonide 100 microg or 200 microg daily, or placebo for 27 months. All participants were asked to inhale medication or placebo from two different Turbuhalers (morning and evening) during the study. A total of 122 children (80 boys, 42 girls) aged 7-16 years with mild asthma (mean FEV(1) 103.7% of predicted) were included in the trial. Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals. RESULTS: A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months, reaching mean values of 40.6% and 46. 9% for inhaled morning and evening medication respectively. Drug adherence declined more rapidly in the placebo group (compared to active treatment); this difference became significant after two years of treatment. Children aged 9 years or less had better drug adherence during the entire study period, but the difference was only significant for the first three months of the study. Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months. CONCLUSION: Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial. This emphasises the importance of monitoring compliance in clinical trials.     

IgE介导的哮喘患儿呼出气一氧化氮水平与气道可逆性的相关性

目的 探讨IgE介导的哮喘患儿呼出气一氧化氮（FeNO）与气道可逆性的相关性。方法 选取2016年9月至2018年8月初诊为哮喘急性发作的6~14岁患儿86例为研究对象,根据血清特异性IgE结果分为IgE介导组（n=61）及非IgE介导组（n=25）,根据过敏原检测结果将IgE介导组进一步分为1、2、3种和4种及以上过敏原阳性组。检测FeNO水平及支气管舒张试验前后常规通气肺功能指标,采用Pearson相关性分析对FeNO与肺功能各项指标进行相关性分析。结果 IgE介导组的FeNO水平明显高于非IgE介导组（P < 0.05）;FeNO水平随着血清特异性过敏原阳性种类的增加而增加（P < 0.05）;IgE介导组FeNO与支气管舒张试验用药前后第1秒末用力呼气量（FEV1）的改变量（△FEV1）和改善率（△FEV1% pred）呈正相关（分别r=0.655、0.473,P < 0.05）,而与FEV1、FEV1占预计值百分比（FEV1% pred）、呼气峰流速（PEF）、用药前后PEF的改变量（△PEF）和改善率（△PEF% pred）、PEF占预计值的百分比（PEF% pred）无相关性（P > 0.05）;非IgE介导组FeNO与上述指标均无相关性（P > 0.05）。结论 FeNO水平与过敏程度有关;对于IgE介导的哮喘患儿,FeNO水平与气道可逆性存在正相关,对哮喘的诊断、评估病情及了解气道可逆性有一定价值;对于非IgE介导的哮喘患儿,FeNO则不适用于间接了解其气道可逆性,两者需区别对待。     

Early intervention of recent onset mild persistent asthma in children aged under 11 yrs: the Steroid Treatment As Regular Therapy in early asthma (START) trial

Inhaled corticosteroids are known to be effective in persistent asthma, but their long-term effect in mild persistent disease of recent onset, which is particularly relevant in children, requires clarification. The objective of this study was to determine the long-term efficacy of regular inhaled low-dose budesonide in children aged <11 yrs with mild persistent asthma with onset within 2 yrs of enrollment. Children aged 5–10 yrs formed part of the population of the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study, and they were randomized in a double-blind manner to treatment with once daily budesonide 200  μ g or placebo via Turbuhaler^TM in addition to usual clinical care and other asthma medication. The double-blind treatment phase continued for 3 yrs. Of the 1974 children, 1000 in the budesonide group and 974 in the placebo group, were analyzed for efficacy. Addition of once-daily budesonide to usual care was associated with a significant increase in the time to first severe asthma-related event (SARE) and significantly reduced risk of SARE over 3 yrs. The hazard ratio relative to usual care (placebo) was 0.60 (95% confidence interval: 0.40–0.90; p = 0.012), with a relative risk reduction of 40%. Children receiving budesonide also needed significantly less intervention with other inhaled corticosteroids (12.3% vs. 22.5% over 3 yrs; p < 0.01), with trends towards decreased usage of oral/systemic corticosteroids and inhaled short-acting β ₂-agonists. Budesonide treatment also had a significant beneficial effect on lung function relative to placebo. In conclusion, early intervention adding once-daily budesonide to usual care in children with mild, persistent asthma of recent onset reduces the long-term risk and frequency of SAREs and improves lung function compared with usual care alone.     

Assessment of quality of life in asthmatic Turkish children

Our aim was to assess impairment in quality of life (QOL) in asthmatic children and to determine the influencing factors. The study group consisted of 305 outpatients with asthma, aged 7-17 years, who were undergoing regular checkups in our outpatient clinic. QOL was assessed using the Pediatric Asthma QOL Questionnaire (PAQLQ). Asthma severity, presence of allergic rhinitis, and steroid usage were strongly and negatively associated with the overall PAQLQ score (p = 0.038) in multivariate regression models. Sex, IgE levels, positive skin tests and smoking status demonstrated no statistically significant effects on the overall or three individual domain PAQLQ scores (p = 0.307, 0.137, 0.470, 0.353, respectively). Lung function measures were strongly correlated with each other (Spearman correlation of 0.77), but were not associated with QOL (p = 0.441). Fifty-one percent of the patients reported that asthma affected their lives significantly. This study captured the baseline QOL information about the pediatric asthmatic population and factors influencing QOL and will facilitate longitudinal monitoring.     

Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma

OBJECTIVE: To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma. STUDY DESIGN: Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks. RESULTS: Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49). CONCLUSION: FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.     

A once daily theophylline preparation in prevention of nocturnal symptoms in childhood asthma

Twenty school children with chronic asthma who despite regular prophylactic therapy continued to have trouble-some nocturnal wheeze or cough entered a double-blind cross-over study in which a once daily theophylline preparation was compared with placebo to assess control of these symptoms. Seventeen children completed both phases of the study. Significant improvement was noted in the day and night symptom scores, the morning dip index and daily peak flow readings with a significant reduction in rescue bronchodilator inhaler usage during the active treatment period. Satisfactory serum theophylline concentrations were obtained 11–12 h post dose in all children using a standard dose of 18 mg/kg per day at 2000 hours. Three children were withdrawn because of minor side-effects. The theophylline preparation studied in conjunction with other conventional anti-asthma therapy was thus effective in controlling nocturnal symptoms.Abbreviations MDI morning dip index - SRT slow release theophylline - SCG disodium cromoglycate - PFR peak flow rate     

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.     

Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study).

OBJECTIVE: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and INTERVENTIONS: 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. MAIN OUTCOME MEASURES: Lung function, the number of exacerbations and growth. RESULTS: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. CONCLUSIONS: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.     

A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants

RATIONALE: Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States. METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma. Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients. RESULTS: Patients enrolled had an average duration of asthma of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo. CONCLUSION: Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.     

Lung function and asthma symptoms in children: relationships and response to treatment

The aim of this study was to determine the relationships between the forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and asthma symptom scores, as well as their response to treatment, in children with no recent exacerbations of asthma. Asthma symptom scores, FEV1 and PEF were characterised, and their relationships and changes at follow-up studied in 64 children (mean age 9.5 y) referred to asthma outpatients. The mean FEV1 and PEF at the initial clinic visit were 94% of predicted values. At follow-up, mean FEV1 and PEF were similar. However, symptom scores (maximum obtainable score for each variable = 3) for exercise, nocturnal cough and morning cough were abnormal at the initial visit (mean +/- SD, exercise 1.0 +/- 0.7, nocturnal cough 1.7 +/- 1.2, morning cough 1.6 +/- 1.2) and improved significantly at follow-up (exercise 0.8 +/- 0.7, nocturnal cough 0.9 +/- 1.1, morning cough 1.0 +/- 1.2) (p < 0.05). A significant relationship was not observed between lung function and total symptom score, at either the initial or follow-up clinic visit. Neither FEV1 nor PEF significantly correlated with individual symptom scores. While symptom control improved, no significant relationships between change in asthma symptom scores and change in FEV1 and PEF between the initial and follow-up visits were observed. CONCLUSION: Clinic ("office") spirometry, currently performed world-wide, cannot be uniformly regarded as an indicator of asthma status. In addition to the measurement of lung function, quantitative symptom scoring may be a helpful tool for physicians in the assessment of childhood asthma status.