University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• My patient is a 19 month old boy with stable asthma, with a history of 4 exacerbations requiring oral steroids. His parents complain that BID dosing with a nebulizer is time-consuming and very difficult to accomplish with an active, independent toddler. In infants and toddlers with asthma, is administration of daily maintenance corticosteroid therapy with MDI/spacers a reasonable alternative to nebulizers?

Clinical Bottom Lines

1. Randomized, controlled data assessing long-term management of asthma in toddlers using MDIs for administration of maintenance corticosteroid therapy is not available.
   
2. Randomized, controlled data assessing complications of long-term exposure to aerosolized corticosteroid therapy is not available.
   
3. MDI/ spacers are more compact, do not require electricity, are cheaper, and more efficient than nebulizer machines for the delivery of aerosolized maintenance therapy.
   
4. MDI/ spacers, (detergent-treated or metal, to eliminate electrostatic charge) operated by parents in their homes (“in vivo”), are able to deliver a substantial fraction of an actualized dose of aerosolized corticosteroid into the mouths of toddlers, with considerable dose-to-dose variability but good mean delivery averaged over a week.1
   
5. Using MDI/ spacers (detergent-treated or metal, to eliminate electrostatic charge) in a laboratory setting (“in vitro”) it is possible to deliver a substantial fraction of an actualized dose of aerosolized labeled corticosteroid into the lungs of toddlers.2
   
6. Fluticasone 44ug 2 puffs BID was prescribed; an MDI/spacer should improve compliance and appears (although conclusions are limited by the lack of randomized, controlled long-term data) to provide comparable dose delivery; fluticasone has lower GI absorption than budesonide; 2 puffs BID of low dose was prescribed to address the high level of dose-to-dose variability; and parents were instructed to wash the spacer in detergent and drip-dry it.

Summary of Key Evidence

1. In a randomized crossover study, children with stable asthma, including 9 toddlers (age 17 to 37 months) and a total of 17 preschoolers, were administered budesonide 200ug BID x 2 weeks at home by their parents using MDIs with two different spacers (the Nebuchamber, made of metal, and the Babyhaler, polycarbonate and detergent treated) each for one week.1
2. Dispensed aerosol was collected from each actuation on filters positioned between face-mask and spacer. These filters (14 for each week and spacer) were analyzed for budesonide dose. Filter doses were averaged over each week (for each spacer), and average filter doses, reported as percentages of the nominal dose (200ug) as well as coefficients of variation were calculated for each subject.
3. Asthma symptoms and level of cooperation were recorded in a diary over the course of the study, and were scored from 0 to 3. Data was processed for all filters (n=476) and then re-processed to exclude filters which were collected with poor cooperation scores (2 or 3) (n=41). Either way the outcome was the same. Also, when mistakes were made in drug administration, either recorded in the diaries or inferred by filter doses of 0% or >100%, these filter doses were not excluded from the analysis.
4. There was extremely broad within-subject variability in the 1 to 4 year-olds, with coefficients of variation of 34.1 +/- 15.6 for the Nebuchamber and 37.2 +/-5.0 for the Babyhaler, but the mean filter doses were substantial at 41.7% +/- 10.1% and 26.0% +/- 4.0%, respectively, of the nominal dose of 200ug of budesonide.
5. Mean filter doses were significantly higher in the Nebuchamber than in the Babyhaler (p<0.0001).
   

Additional Comments

• In a comparison of filter deposition of salbutamol administered to wheezy infants aged 4 to 12 months with either a nebulizer (Pari-Baby) or MDI/spacer (Nebuchamber or detergent-coated Babyhaler), the mean deposition was only 25.3% of the total nebulized dose, but was 40.2% and 40.7% for the MDI/spacers.3
• In 15 infants and toddlers (age range 3 months to 5 years), technetium-labeled salbutamol was administered by MDI and spacer (non-detergent treated Aerochamber). Most of the actuated dose remained in the spacer, with a distribution of 1.97 +/-1.4% in the lungs, 1.28 +/-0.77% in the oropharynx, and 1.11 +/-2.4% in the stomach. This was compared with two adult controls with 19% in the lungs and 2% in the stomach.4
• In 8 children between the ages of 1 and 4 years, technetium-labeled salbutamol was administered by MDI and spacer (detergent-treated Babyhaler). Mean deposition of the actuated dose was 16.4% +/-5.5% in the lungs, 20.9% +/- 5.1% in the GI system (mouth, throat, esophagus, and stomach). For comparison, 5 children aged 8 to 12 years had lung deposition of 41.8% +/- 3.8% and GI deposition of 16.5% +/- 3.0%.2

Citation

1. Janssens HM, Devadason SG, Hop WCJ, LeSouef PN, De Jongste JC, Tiddens HAWM. Variability of aerosol delivery via spacer devices in young asthmatic children in daily life. Eur Respir J 1999; 13:787-791.
2. Wildhaber JH, Janssens HM, Pierart F, Dore ND, Devadason SG, and LeSouef PN. High-percentage lung delivery in children from detergent-treated spacers. Pediatric Pulmonology 2000; 29:389-393.
3. Wildhaber JH, Devadason SG, Hayden MJ, Eber E, Summers QA, LeSouef PN. Aerosol delivery to wheezy infants: A comparison between a nebulizer and two small volume spacers. Pediatric Pulmonology 1997; 23:212-216.
4. Tal A, Golan H, Grauer N, Aviram M, Albin D, Quastrel MR. Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction. J Pediatr 1996; 128:479-484.

CAT Author: Randall Phelps, MD, PhD

CAT Appraisers: Katherine L. Layton, MD

Date appraised: <List Journal Club Date here>