Randomized comparison of a dry powder inhaler and metered dose inhaler with spacer in management of children with asthma

OBJECTIVE: Comparison of the clinical efficacy of a transparent, DPI (transparent Rotahaler) with MDI and spacers in childhood asthma. DESIGN: Open, randomized, crossover trial. SETTINGS: Out patient clinic of a referral pediatric center. METHODS: Thirty (mean 6.1 +/-2.7 years) children with moderate persistent asthma were randomized to receive long-term medications by a DPI or a metered dose inhaler with spacer for six weeks and then crossed over to receive the same drugs for another period of six weeks after an initial run in period of one week for training in inhalation techniques. The preventative therapy consisted of inhaled Beclomethasone dipropionate (600 mcg/day) and Salbutamol as per requirement. The patients were monitored by a symptom diary, weekly PEFR, and PEFR variability by the parental record of PEFR measurements at home with Mini Wright s Peakflow meter in accordance with the Consensus guidelines. RESULTS: Comparisons made on weekly symptom scores, PEFR at interval visits, PEFR variability, additional beta sympathomimetic use and acute exacerbations of asthma did not reveal any statistically significant differences during the two treatment periods (>0.05). CONCLUSION: Metered dose inhaler and dry powder inhaler have equal efficacy in anti-inflammatory therapy of bronchial asthma in children.     

Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.

OBJECTIVE: In children with mild acute asthma, to compare treatment with a single dose of albuterol delivered by a metered dose inhaler (MDI) with a spacer in either a weight-adjusted high dose or a standard low-dose regimen with delivery by a nebulizer. STUDY DESIGN: In this randomized double-blind trial set in an emergency department, 90 children between 5 and 17 years of age with a baseline forced expiratory volume in 1 second (FEV1 ) between 50% and 79% of predicted value were treated with a single dose of albuterol, either 6 to 10 puffs (n = 30) or 2 puffs (n = 30) with an MDI with spacer or 0.15 mg/kg with a nebulizer (n = 30). RESULTS: No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups. CONCLUSION: In children with mild acute asthma, treatment with 2 puffs of albuterol by an MDI with spacer is just as clinically beneficial as treatment with higher doses delivered by an MDI or by a nebulizer.     

The tube spacer in children with asthma

ABSTRACT. We compared the use of a standard metered aerosol actuator with the tube spacer in delivering 500 micrograms of terbutaline sulphate to the airways of seven children with clinical asthma. Each child used the standard metered aerosol in his usual way and the tube spacer with a 5 second delay between actuation and inhalation on separate occasions. Response was measured by change in forced expiratory volume in one second (FEV₁). We found no significant difference in bronchodilatation between the two methods of aerosol delivery. We conclude that the tube spacer is an effective way of delivering a metered aerosol and that it has the advantage of allowing up to 5 seconds between actuation and inhalation. The tube spacer has particular application in young children who have difficulty in co-ordinating their inspiration with metered aerosol actuation.     

Metered-dose inhaler with spacer vs nebulization for severe and potentially severe acute asthma treatment in the pediatric emergency department]

OBJECTIVE: To compare treatment with beta 2 agonist delivered either by a spacer device or a nebulizer in children with severe or potentially severe acute asthma. METHODS: In this randomized trial, children 4 to 15 years, cared for in the emergency department for severe or potentially severe acute asthma, received 6 times either nebulizations of salbutamol (0.15mg/kg) or puffs of a beta 2 agonist (salbutamol 50 microg/kg or terbutaline 125 microg/kg). The primary outcome was the hospitalization rate. Secondary outcomes included percentage improvement in Bishop score, in PEF, SaO(2), respiratory and heart rates, side effects, length of stay and relapses 10 and 30 days later. RESULTS: Groups did not differ for baseline data. There were no significant differences between the 2 groups (nebulizer N=40, spacer N=39) for baseline characteristics before emergency department consultation except for length of acute asthma in the spacer group. Clinical evolution after treatment, hospitalization rate, relapse were similar including the more severe subgroup. In the spacer group, tachycardia was less frequent (P<0.02). The overall length of stay in the emergency department was significantly shorter (148+/-20 vs 108+/-13 min, P<10(-9)). CONCLUSIONS: The administration of beta 2 agonist using a metered-dose inhaler with spacer is an effective alternative to nebulizers for the treatment of children with severe or potentially severe acute asthma in the emergency department. Time gained can be used for asthma education.     

Comparative efficacy of terbutaline sulphate delivered by Turbuhaler dry powder inhaler or pressurised metered dose inhaler with Nebuhaler spacer in children during an acute asthmatic episode.

AIMS: To compare the efficacy of terbutaline sulphate delivered via Turbuhaler with a pressurised metered dose inhaler (pMDI) connected to Nebuhaler spacer in a population of asthmatic children presenting to emergency departments because of an acute episode of asthma. METHODS: Randomised double blind, double dummy, parallel study of acute asthma in the emergency department. A total of 112 children (6-16 years), who had a diagnosis of asthma, a baseline FEV1 of 25-60% of predicted normal value (PNV), and the ability to perform spirometry were studied. Patients received two doses of 0.5 mg/10 kg (maximum 2.0 mg) of terbutaline sulphate at time 0 minutes and time 30 minutes. The two groups were also stratified into subgroups based on FEV1: 25-45% and 45.1-60% PNV. FEV1 before treatment and at two 15-minute intervals after each treatment was the main outcome measure. PIF, PEF, heart rate, SpO2, and tremor were also measured at these times. RESULTS: Both the Turbuhaler and pMDI+Nebuhaler groups showed significant increases from baseline to final value in their FEV1 results, 49% and 50% change from baseline to t = 60 min, respectively (p < 0.001) using last value carried forward. No significant difference was found between the two groups for these results. Subanalysis of the stratified groups revealed similar results. In addition, no significant difference was found in the group and subgroup comparisons for heart rate, SpO2, and tremor. CONCLUSION: Results show that Turbuhaler and pMDI+Nebuhaler are similar in terms of benefit and side effects in the treatment of acute moderate to severe asthma attacks in this study population.     

Comparative efficacy of terbutaline sulphate delivered by Turbuhaler dry powder inhaler or pressurised metered dose inhaler with Nebuhaler spacer in children during an acute asthmatic episode

Aims: To compare the efficacy of terbutaline sulphate delivered via Turbuhaler with a pressurised metered dose inhaler (pMDI) connected to Nebuhaler spacer in a population of asthmatic children presenting to emergency departments because of an acute episode of asthma. Methods: Randomised double blind, double dummy, parallel study of acute asthma in the emergency department. A total of 112 children (6–16 years), who had a diagnosis of asthma, a baseline FEV₁ of 25–60% of predicted normal value (PNV), and the ability to perform spirometry were studied. Patients received two doses of 0.5 mg/10 kg (maximum 2.0 mg) of terbutaline sulphate at time 0 minutes and time 30 minutes. The two groups were also stratified into subgroups based on FEV₁: 25–45% and 45.1–60% PNV. FEV₁ before treatment and at two 15-minute intervals after each treatment was the main outcome measure. PIF, PEF, heart rate, SpO₂, and tremor were also measured at these times. Results: Both the Turbuhaler and pMDI+Nebuhaler groups showed significant increases from baseline to final value in their FEV₁ results, 49% and 50% change from baseline to t = 60 min, respectively (p < 0.001) using last value carried forward. No significant difference was found between the two groups for these results. Subanalysis of the stratified groups revealed similar results. In addition, no significant difference was found in the group and subgroup comparisons for heart rate, SpO₂, and tremor. Conclusion: Results show that Turbuhaler and pMDI+Nebuhaler are similar in terms of benefit and side effects in the treatment of acute moderate to severe asthma attacks in this study population.     

A 500‐ml plastic bottle: An effective spacer for children with asthma

Inhaled therapy using a metered‐dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI‐spacer delivery systems. A 500‐ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle‐spacer and discusses its advantages and limitations. It is concluded that a modified 500‐ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.     

Bronchodilator aerosol administered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome.

There is increasing evidence that bronchodilators are effective in ventilator dependent preterm infants. The effects of single doses of salbutamol (400 micrograms), ipratropium bromide (72 micrograms), and placebo (four puffs) given by metered dose inhaler and spacer (MDIS) were examined in 10 ventilated preterm infants, with a mean birth weight of 800 g at a postnatal age of 1 week, who were suffering from respiratory distress syndrome. The agents were each given in an open, random design. Blood gases were measured and ventilatory efficiency index (VEI) and arterial/alveolar oxygen tension ratio (PaO2/PAO2) were calculated five minutes before and 30 minutes after administration. Heart rate and mean arterial blood pressure were noted. The mean PaO2 improved by 0.61 kPa and 0.69 kPa after salbutamol and ipratropium bromide, respectively and these changes were significantly greater than the 0.5 kPa fall seen with placebo. The mean arterial carbon dioxide tension fell by 0.98 kPa after salbutamol and 0.59 kPa after ipratropium bromide. After both salbutamol and ipratropium bromide, VEI improved significantly (by 23% and 20% respectively) but there was no significant change in the PaO2/PAO2, suggesting that respiratory mechanics and not ventilation/perfusion balance had improved after a single dose of bronchodilator. We conclude that both salbutamol and ipratropium bromide given by MDIS have useful short term effects in ventilator dependent neonates with respiratory distress syndrome. Precise dose regimens and long term effects remain to be worked out.     

Application and efficacy of the multi‐dose powder inhaler, Easyhaler®, in children with asthma

With powder inhalers, optimal performance is dependent on the inspiratory flow produced by the patient through the devices. The objective of this open, non‐randomized study was to evaluate the suitability of a new, multi‐dose, dry powder inhaler, the Easyhaler^®, for children with asthma. The peak inspiratory flow (PIF) through the Easyhaler (PIF_EH) was measured with a pneumotachograph in 120 asthmatic children aged 4–16 yr. The bronchodilatory effect of 0.2 mg salbutamol through the Easyhaler was compared with that of 0.2 mg salbutamol through a metered dose inhaler (MDI) with a spacer, in 15 children with obstruction. The mean PIF_EH was 56 l/min (range 22–83 l/min). The PIF_EH correlated significantly with age, height, and absolute peak expiratory flow (PEF), but not with the level of obstruction (PEF percentage of predicted, range 45–146%). Only four children (aged 5, 6, 10, and 16 yr) had PIF_EH values below 28 l/min, which has been shown in in vitro studies to be the threshold for effective use of the Easyhaler. In 15 children with PEF, < 85% of predicted bronchodilatory effects of 0.2 mg salbutamol through the Easyhaler and from an MDI‐cum‐spacer were equal. Most children aged 6–16 yr produce PIF values sufficient for the use of the Easyhaler. The gain of 0.2 mg salbutamol from the Easyhaler was equal to that from a new, unprimed, MDI with a spacer in children with asthma.     

Influence of spacer device on drug delivery to young children with asthma.

The budesonide dose delivered to the patient from three different spacer devices (Nebuhaler = 750 ml, Aerochamber = 140 ml, and Babyspacer = 260 ml) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient. Twenty children aged 10-25 months were given a single dose of 200 micrograms budesonide from each spacer device in a randomised crossover study. All spacers had a facemask attached and a one way valve system. The children breathed through the inhalation system for 30 seconds. Furthermore, the minute ventilation of the children through a tightly fitting facemask was measured. The filter dose of budesonide was significantly lower after Aerochamber treatment (39.4 micrograms, range 19-67 micrograms) than after Nebuhaler (53.5 micrograms, range 34-88 micrograms) and Babyspacer (55.5 micrograms, range 39-76 micrograms) treatment. The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min (mean 5.0 l/min). This was sufficient to empty all spacers within the 30 seconds of inhalation. It is concluded that spacer volume does not seem to be so important for children aged 10-25 months as long as spacers with a volume lower than 750 ml are used.     

Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack

Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma.     

Salmeterol/fluticasone propionate vs. double dose fluticasone propionate on lung function and asthma control in children

There is a large body of data to support the use of an inhaled corticosteroid (ICS) plus a long‐acting β₂‐agonist vs. increasing the dose of ICS in adults, but less data in children. This double‐blind, parallel group, non‐inferiority study compared lung function and asthma control, based on Global Initiative for Asthma guidelines, in children receiving either salmeterol/fluticasone propionate (SFC) 50/100 μg bd (n = 160) or fluticasone propionate (FP) 200 μg bd (n = 161) for 12 wks. Change from baseline in mean morning peak expiratory flow increased following both treatments, but was significantly greater in the SFC group compared with FP [Adjusted mean change (s.e.) (l/min): SFC: 26.9 (2.13), FP: 19.3 (2.12); treatment difference: 7.6 (3.01); 95% CI: 1.7, 13.5; p = 0.012)]. Asthma control improved over time in both groups. Mean pre‐bronchodilator maximal‐expiratory flow at 50% vital capacity and percentage rescue‐free days showed significantly greater improvements in the SFC group compared with FP. All other efficacy indices showed comparable improvements in each group. Treatment with SFC 50/100 μg bd compared with twice the steroid dose of FP (200 μg bd), was at least as effective in improving individual clinical outcomes and overall asthma control, in asthmatic children previously uncontrolled on low doses of ICS.     

Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction.

BACKGROUND: Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. OBJECTIVE: To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer METHODS: A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI-spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. RESULTS: 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). CONCLUSION: A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.