Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics. A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma. Drug delivery and adherence in young children. The effect of nebulized budesonide treatment in children with mild to moderate exacerbations of asthma. Controlled trial of budesonide given by the nebuhaler in preschool children with asthma. Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment. Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma. Effect of an intranasally administered corticosteroid (budesonide) on nasal obstruction, mouth breathing, and asthma. Use of spacers to facilitate inhaled corticosteroid treatment of asthma.
The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients. A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment. In actual fact, the apparent order of effect was: 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device. The adverse effects reported appeared to be related to the dose rather than delivery device. Accordingly, the effect was related to total mass output, rather than to the small particle fraction of the budesonide aerosol. These results attest to the efficiency of jet-nebulized budesonide suspension, and indicate nebulized budesonide to be equipotent to standard budesonide therapy delivered by pMDI with Nebuhaler, provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration. Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.
                The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.
                This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.
                Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.
                This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma. The aim of this pilot study was to compare a the HaloLite Paediatric Nebulizer (HPN) with a pressurized metered dose inhaler and valved holding chamber (pMDI VHC, Aerochamber) in terms of drug delivery, adherence to treatment, compliance with device, true adherence, and acceptability. Fourteen children aged 11-36 months with asthma on regular treatment with inhaled corticosteroids were enrolled into an open, randomized, crossover trial. They received budesonide for 2 weeks with each delivery system. Both devices incorporated a datalogger which recorded information on how the device was used. The HPN was preprogrammed to deliver 25 microg of budesonide to the patient. A single actuation of budesonide 200 microg was used with the pMDI VHC. The median delivered dose of budesonide was 36 microg (range, 31-45 microg; CV, 15%) for the HPN and 53 microg (range, 17-85 microg; CV, 47%) for the pMDI VHC. The median adherence was 68% (range, 11-96%) with the HPN and 71% (range, 11-100%) with the pMDI VHC. The median device compliance was 30% and 51% and the median true adherence was 23% and 36%, respectively. The shape, size, and weight of the HaloLite Paediatric Nebulizer were generally less acceptable than the shape, size, and weight of the pMDI VHC with datalogger. These results indicate that reproducible quantities of drug can be delivered to very young children using AAD technology such as that incorporated into the HPN. Drug delivery with the pMDI VHC was more variable, but parents preferred this device.
                Copyright 2004 Wiely-Liss, Inc. The role of inhaled corticosteroids in the treatment of acute asthma remains a controversial subject.
                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.
                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.
                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. To determine whether the inhaled corticosteroid budesonide, given by a Nebuhaler spacing device, was effective in prophylaxis of asthma in preschool children.
                Double blind, placebo controlled, random order crossover trial with two week practice run in period.
                Outpatient clinic referrals in secondary referral centre.
                39 children aged 2-6 years selected for the following: able to use Nebuhaler; parents able to complete record card; poorly controlled asthma (defined); not already on systemic or inhaled steroids. Eleven withdrew for various reasons not connected with intolerance to budesonide. Age, sex, other atopies, and symptoms during run in period were similar in the 28 children who completed the trial and in the 11 who withdrew.
                Budesonide 200 micrograms or placebo (both one puff) given twice daily during 6-week treatment or control periods, using Nebuhaler after prior training. Three week "washout" at crossover. Compliance monitored by weighing canisters. Patients withdrawn if their acute attacks required treatment with systemic steroids.
                Control of asthma.
                Peak expiratory flow rate measured twice daily where cooperation allowed. Diary of symptoms and concomitant drug use kept daily. Results showed mean peak flow significantly higher (12% in mornings, 14% in evenings) in second three weeks of intervention compared with control period (95% confidence intervals 6.3-17.3% and 7.2-21.0%). Supplementary bronchodilator drugs reduced by 50% during intervention periods.
                Budesonide given by Nebuhaler is effective prophylaxis for preschool children with frequent asthma. New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive patients with asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients. Forty patients started with 400 microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline, and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53), respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma. In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled beta 2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from beta 2-agonist therapy to corticosteroid therapy would have.
                A total of 37 patients treated for two years with inhaled budesonide at a dose of 1200 micrograms per day were randomly assigned to treatment with 400 micrograms of budesonide per day (19 patients) or placebo (18 patients) in a double-blind manner. Another 37 patients, who had received terbutaline during the first two years, were crossed over in an open-label manner to treatment with 1200 micrograms of budesonide per day during the third year.
                Treatment with the reduced dose of budesonide was sufficiently effective in 74 percent of the patients to maintain bronchial responsiveness at a level similar to that achieved with the higher dose. In contrast, improvement was maintained in only 33 percent of the patients receiving placebo, and the differences in pulmonary function between the steroid and placebo groups were significant (for forced expiratory volume in one second, P = 0.007; for bronchial responsiveness to histamine, P = 0.025; and for peak expiratory flow in the morning, P = 0.040). The condition of patients who were crossed over from terbutaline therapy to treatment with 1200 micrograms of budesonide per day improved. However, the degree of improvement in these patients appeared to be less than in those who were treated with budesonide at the beginning of the three-year study.
                Early treatment with inhaled budesonide results in long-lasting control of mild asthma. Maintenance therapy can usually be given at a reduced dose, but discontinuation of treatment is often accompanied by exacerbation of the disease. The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma. Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.
Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that still require further assessment. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.