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 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.
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.