Objective. The availability of antiinflammatory asthma medications for infants and young children has been limited. The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma.Methods. We conducted a randomized, parallel-group, 52-week, open-label study in 36 US clinical sites. Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication; 287 children (86%) completed the study. Patients received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed by dose titration at the investigator's discretion. The main outcome measure was the rate of asthma exacerbations over 52 weeks. Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy, asthma symptom scores, rescue medication use, and health care resource use.Results. The budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per year compared with 2.41 (1.85) for the cromolyn group, significantly longer times to first exacerbation and first use of additional long-term asthma medication, greater improvements in asthma symptom scores, reduced use of rescue medication, and fewer urgent care visits. Both treatments were well tolerated.Conclusions. Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma. Both treatments were well tolerated with similar adverse event profiles.

Background: The initial 12-week, double-blind phases of three studies demonstrated that budesonide inhalation suspension (BIS) is effective and well tolerated in infants and young children (6 months to 8 years of age) with persistent asthma.Objective: Open-label, 52-week extensions to these studies were conducted to evaluate long-term safety of BIS, including effects of treatment with the lowest effective dose of BIS on hypothalamic-pituitary-adrenal (HPA)-axis function, as compared with conventional asthma therapy (CAT). Complete results of the earlier phases of the studies and of long-term safety are reported elsewhere; only results pertaining to HPA-axis function are summarized here.Methods: Patients eligible for the open-label phases of the three trials were randomized to treatment with nebulized BIS (n = 447) or CAT (n = 223). CAT included short-acting oral or inhaled beta(2)-agonists, methylxanthines, or cromolyn sodium; in two of the studies, CAT could have included other inhaled corticosteroids. HPA-axis function, which had been evaluated during the 12-week double-blind studies, was again evaluated at the beginning and end of the 52-week study period using basal plasma cortisol concentrations and response to stimulation with a 250-mug dose of adrenocorticotropic hormone.Results: There was no evidence of altered HPA-axis function attributable to BIS treatment. No clinically or statistically significant differences in basal or adrenocorticotropic hormone-stimulated plasma cortisol concentrations were observed between BIS and CAT in either the 12-week, double-blind or 52-week, open-label phases of the three studies.Conclusions: The results indicate that treatment with BIS does not result in clinically significant suppression of HPA-axis function in infants and young children.

A retrospective analysis, based on a randomized, placebo-controlled, 12-week study in children 6 months to 8 years of age with persistent asthma, was performed to compare the efficacy and safety of budesonide inhalation suspension 0.25 mg and 0.5 mg twice daily vs. placebo in children <4 and ≥4 years of age. Both age groups demonstrated significant (p ≤ 0.050) improvement in nighttime and daytime asthma symptom scores and decreased bronchodilator use compared with placebo. In addition, the safety profile of twice-daily budesonide inhalation suspension was favorable in both age groups.

This study is a retrospective analysis comparing nebulized budesonide inhalation suspension (BIS; Pulmicort Respules™, AstraZeneca, Wilmington, DE) administered once daily by facemask or mouthpiece in 359 infants and young children with persistent asthma. The efficacy and safety of once-daily BIS (0.25, 0.5, and 1.0 mg) administered by facemask or mouthpiece were demonstrated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study reported by Kemp et al. (Ann Allergy Asthma Immunol 1999; 83:231–239). Three hundred fifty-nine children aged 6 months to 8 years with mild, persistent asthma received nebulized BIS 0.25, 0.5, or 1.0 mg once daily or placebo for 12 weeks via facemask or mouthpiece. Efficacy variables included nighttime and daytime asthma symptom scores, use of breakthrough bronchodilator medications, and pulmonary function tests (in children capable of consistently performing spirometry or peak flows). Changes in nighttime and daytime asthma symptom scores were not significantly different between children using facemasks and those using mouthpieces. Use of breakthrough medications and pulmonary function test results (in the subset of children able to perform them) also were not significantly different in facemask users and mouthpiece users. These results suggest that BIS is equally effective whether administered by facemask or mouthpiece and that young children who require the use of a facemask may be successfully treated.

Background: Budesonide inhalation suspension (Pulmicort Respules: Astra-Zeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. Objective: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children <4 years of age and in those greater than or equal to4 years of age with persistent asthma. Methods: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. Results: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children <4 years of age at the 0.25-mg dose level. Conclusions: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged <4 and greater than or equal to4 years of age.

Background: Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children.Objective: Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations.Methods: Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 9.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined.Results: In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1.0 mg and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (-0.19, P =.003), and there was a small, statistically significant decrease in growth velocity (-0.8 cm/y, P =.002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C.Conclusion: There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children.

Background: Inhaled glucocorticosteroids (GCS) are the most effective longterm controller medications for the treatment of persistent asthma. Currently, however, available delivery devices limit their use in young children. A nebulized formulation of budesonide has been developed to address the needs of infants and young children.Objective: To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS.Methods: Three hundred fifty-nine children were randomized to receive once-daily budesonide inhalation suspension (0.25 mg, 0.50 mg, or 1.0 mg) or placebo via a Pari LC-Jet Plus(TM) nebulizer for 12 weeks. Efficacy assessments included nighttime/daytime asthma symptoms, pulmonary function (subset of patients), rescue medication use, and treatment discontinuations. Safety was based on adverse events and assessment of HPA-axis function.Results: Demographics, baseline characteristics, asthma symptoms, and pulmonary function were similar across treatment groups. Mean nighttime/daytime asthma symptom scores were 1.19 +/- 0.63 and 1.34 +/- 0.53, respectively. Mean duration of asthma was 36.3 months and mean FEV1 was 81.3% of predicted with 27.7% reversibility.Following 12 weeks of treatment, all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms (P less than or equal to.049) and significant decreases in rescue medication use (P less than or equal to.038) compared with placebo. Significant improvements (P less than or equal to.044) in FEV1, were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups. There were no differences between doses of budesonide inhalation suspension. Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups.Conclusion: Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments.