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 µg or 200 µg 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 FEV₁ 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.

     

Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid

OBJECTIVE: To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma. DESIGN: Randomised, double blind, placebo controlled, crossover trial. METHODS: Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose. RESULTS: There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo. CONCLUSION: This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.     

Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid

OBJECTIVE—To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.
DESIGN—Randomised, double blind, placebo controlled, crossover trial.
METHODS—Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.
RESULTS—There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (−3.5% to 10.4%) and −0.9% (−4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents'' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.
CONCLUSION—This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.

     

Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.

AIMS: To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids. METHODS: A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance. RESULTS: Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen. CONCLUSION: These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.     

Effect of placebo substitution during long-term betamethasone valerate aerosol treatment in asthmatic children.

Ten children with severe asthma, who had been well controlled on maintenance betamethasone valerate aerosol for an average of 11 months, were given placebo aerosols without their knowledge. The period of placebo substitution was campared with one 28-day period of betamethasone valerate therapy beforehand, and two 28-day periods afterwards. Symptoms were increased during the placebo period, and patients did not return to their previous well-controlled state until the second month after reinstitution of therapy. Changes in the means of twice-daily peak expiratory flow readings (PEFR) followed the same pattern as changes in symptoms. The exacerbation of asthma which occurred during placebo treatment was accompanied by a widening in the diurnal variation between morning and evening PEFR. In comparison with the previous period, morning PEFR fell by a greater amount than evening PEFR. Standardized running tests suggest an increase in exercise-induced bronchoconstriction and in the Exercise Lability Index when the child was receiving only placebo treatment as compared with betamethasone valerate treatment. The trial provided further evidence of the efficacy of betamethasone valerate aerosol in the prophylatic therapy of severe childhood asthma. As 2 of these children were able to discontinue long-term therapy it is unlikely that this drug causes dependency.     

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.     

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.     

Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial.

Traditional Chinese medicine has a long history of application in the treatment of bronchial asthma. Solid scientific evidence, however, is not available despite its widespread use among patients worldwide and in Taiwan. To assess the effect of Ding Chuan Tang (DCT) in airway hyper-responsiveness (AHR) on asthmatic children via randomized, double blind, placebo-controlled clinical trial. This study enrolled children who were aged 8-15 and diagnosed as mild to moderate persistent asthma patients. They were randomly allocated to receive 6.0 g DCT or placebo daily for 12 wk. Self-recorded daily symptom scores, medication scores, and morning and evening peak expiratory flow rates were returned at the monthly clinic. Pulmonary function test, methacholine challenge test, and serum inflammatory mediators were measured before and at the end of the trial. Fifty-two asthmatic children completed the clinical study. Twenty-eight patients were assigned to the treatment group and 24 to the placebo group. At the end of the treatment period, AHR determined by log PC(20) was significantly improved in the DCT group (0.51 +/- 1.05 mg/ml vs. 0.26 +/- 0.84 mg/ml, p = 0.034). The total clinical and medication reduced parameters showed improvement in the DCT group (p = 0.004). The AHR, symptom and medication scores in children with persistent asthma were significantly improved with DCT treat for 12 wk. The results suggested more stable airways achieved with such an add-on complementary therapy.     

Intermittent treatment with inhaled steroids for deterioration of asthma due to upper respiratory tract infections

Upper respiratory tract infection (URTI) is a common cause of deterioration of asthma in children. We investigated if inhaled steroids (budesonide), started early after URTI, could reduce asthma. Thirty-one children, 3-10 years of age, with deterioration during URTI participated. The study design was double-blind, crossover and placebo-controlled. Peak-expiratory flow (PEF) and symptom scores were recorded. Four treatment periods of 9 days, two with budesonide and two with placebo, were planned. Treatment was started at the first sign of URTI. Budesonide/placebo was given by Turbuhaler at 0.2 mg qid for 3 days, tid for 3 and bid for the last 3 days. Twenty-two children completed 67 periods. Eleven visited the emergency room, only three during budesonide therapy. Five received oral steroids and two where admitted to hospital, all receiving placebo. Symptom scores were not significantly lower during budesonide treatment. PEF, both morning and evening, was significantly higher during budesonide than placebo (p = 0.015 and p = 0.022). Inhaled budesonide can attenuate exacerbation of URTI-induced asthma. Asthma, budesonide, infection, inhaled steroids, intermittent, prophylactic
J Svedmyr, Department of Paediatrics, Falu Hospital, S-791 82 Falun, Sweden     

Systematic review of the dose-response relation of inhaled fluticasone propionate.

AIMS: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma. METHODS: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. MAIN OUTCOME MEASURES: FEV1, morning peak expiratory flow, night awakenings, beta agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation. RESULTS: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 microg per day with additional efficacy at the 400 microg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 microg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 microg per day. CONCLUSIONS: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 microg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 microg per day for efficacy. There was additional efficacy at the 400 microg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.     

孟鲁司特治疗儿童支气管哮喘的临床疗效观察

目的孟鲁司特联合布地奈德气雾剂吸入治疗合并过敏性鼻炎的轻、中度哮喘儿童临床疗效的前瞻性研究。方法将80例合并有过敏性鼻炎的轻、中度哮喘儿童随机分为治疗组和对照组。治疗组在吸入布地奈德气雾剂的同时加用孟鲁司特片,对照组则在吸入布地奈德气雾剂基础上加安慰剂,其余治疗相同。两组布地奈德气雾剂递减至最适有效剂量(无哮喘症状体征,β2激动剂吸入量无增加,呼气峰流速达预计值的80%以上,或变异率小于20%),并进行统计学分析。结果治疗组在加用孟鲁司特前后布地奈德吸入量减少差异有统计学意义(P<0.05),对照组在加用安慰剂前后布地奈德吸入量减少差异有统计学意义(P<0.05),而且两组比较差异亦有统计学意义(P<0.05)。结论孟鲁司特片联合布地奈德气雾剂治疗儿童合并过敏性鼻炎的哮喘,不仅能明显缓解哮喘和鼻炎的症状,还可以减少糖皮质激素、β2激动剂吸入量,取得了满意的疗效且无明显的不良反应。     

Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study

Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.     

Diurnal leptin rhythms in children treated with prednisolone once daily in the morning or in the evening

Serum leptin levels exhibit a marked diurnal variation in children. The aim of the present study was to investigate whether the timing of administration of exogenous glucocorticoids, which have been found to increase serum leptin, affects the diurnal rhythm. Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with asthma were studied. The design was an open 2-period cross-over trial with a 1-day run in, two 4-day periods of prednisolone 5 mg in the morning or in the evening, with a 3-week washout in between treatment periods. During run in and on the last day of the prednisolone periods a fasting blood sample was drawn at 08.00 h, and thereafter samples were obtained every 2 h throughout the day until 08.00 h the next morning. Serum leptin was measured by a specific radioimmunoassay. During all periods, leptin levels were low during the day with a nadir at 10.00 h (run-in [mean +/- SEM]: 3.9+/-1.28; morning prednisolone: 5.2+/-1.58; evening prednisolone: 5.7+/-2.02 microg/l). Increases in leptin levels were detected from 20.00 h with zeniths at 24.00 h (run in: 7.2+/-1.86; evening prednisolone: 9.2+/-2.36 microg/l) and 02.00 h (morning prednisolone: 9.4+/-1.78 microg/l) (F = 115.5; p <0.01). As compared to run in, leptin levels were increased at all time points during prednisolone treatment in the morning (F = 16.0, p = 0.01) and in the evening (F = 12.6, p = 0.01). No statistically significant differences were found in leptin levels during prednisolone in the morning or in the evening (F = 0.44, p = 0.53). Therefore, the timing of administration of exogenous glucocorticoids does not affect diurnal leptin rhythms in children.     

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.     

The role of inhaled corticosteroids in children with asthma

Inhaled corticosteroids offer a wide range of anti-inflammatory activity and have consistently proved to be the most effective medication for the control of childhood asthma. The high efficacy of inhaled corticosteroids has led to their use in milder disease and younger children in the hope that permanent changes in lung function and airway remodelling may be prevented. However, evidence has emerged over the past six years that the first of the inhaled corticosteroids to become available, beclomethasone dipropionate, may cause growth deceleration at a dose of 400 microg per day. This is especially apparent in children with mild symptoms. The newest of the inhaled corticosteroids to be developed, fluticasone propionate, is equipotent to older compounds at half the dose and in low doses is superior in efficacy to sodium cromoglycate. Two recent studies have shown that fluticasone propionate 100-200 microg per day does not cause growth suppression in children with mild asthma. The long term outcome for children who wheeze in early life is difficult to predict. For this reason the use of inhaled corticosteroids in very young children is best reserved for those with severe symptoms or a strong family history of asthma, and evidence, from measurement of inflammatory markers, of airway inflammation.     

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.     

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.     

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.     

Randomized trial of the addition of ipratropium bromide to albuterol and corticosteroid therapy in children hospitalized because of an acute asthma exacerbation.

OBJECTIVE: To determine whether the addition of inhaled ipratropium bromide to inhaled albuterol and systemic corticosteroid therapy was more efficacious than inhaled albuterol and systemic corticosteroids alone in the inpatient treatment of acute asthma exacerbations in children. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Pediatric inpatient unit of a tertiary urban hospital. PARTICIPANTS: Eighty children (aged 1-18 years) hospitalized because of an acute asthma exacerbation. INTERVENTION: Children were randomized to receive either nebulized ipratropium bromide, 250 microg, or nebulized isotonic sodium chloride solution, 1 mL. All children received albuterol and systemic corticosteroids. MAIN OUTCOME MEASURES: The primary outcome variable was a validated clinical asthma score, measured at baseline and every 6 hours for 36 hours. Secondary outcome measures included the forced expiratory volume in 1 second, the oxygen saturation, the number of doses of inhaled study drug, the time to an inhaled drug-dosing interval of 4 hours, and the length of the hospital stay. RESULTS: There were no differences between groups on baseline characteristics. The intention-to-treat analysis, using repeated-measures analysis of variance, showed no significant (P =.07) difference between the groups in the clinical asthma score over time. There were also no significant differences between groups on secondary outcomes. CONCLUSION: The addition of nebulized ipratropium bromide to nebulized beta(2)-agonist and corticosteroid therapy in the treatment of children hospitalized because of asthma (following intensive emergency department treatment) confers no extra benefit.