title: Drug Delivery in Asthmatic Children Following Coordinated and Uncoordinated Inhalation Maneuvers: A Randomized Crossover Trial.
abstract: BACKGROUND
  Valved holding chambers (VHCs) are used in children to deliver pressurized metered dose inhalers (pMDI). In vitro data suggest that uncoordinated use decreases the amount of drug available for inhalation. We hypothesize that in an ex vivo study, the coordinated maneuver will deliver more drug than the uncoordinated one.
  
  
  METHODS
  Thirty-two clinically stable asthmatic children, ages 5-8 years, completed the study. An aerosol filter was interposed between a small-volume nonelectrostatic VHC and a mouthpiece to capture the drug emitted by one puff of Flovent®220 mcg during tidal breathing. Inhalation and actuation parameters were measured by an electronic monitor, and the number of breaths required to empty the VHC was calculated. Subjects completed three coordinated and three uncoordinated (actuation at the beginning of inhalation and exhalation, respectively) runs in random order. Drug content from the filter and VHC was measured by high-performance liquid chromatography and expressed as percentage of emitted dose.
  
  
  RESULTS
  [mean (99% confidence interval)] Filter dose was higher during coordinated technique 46% (43%-50%) than during uncoordinated technique 41% (37%-44%) (p < 0.001). Peak inspiratory flow and tidal volume were 23.2 L/min (21.3-25.1 L/min) and 281 mL (251-311 mL), respectively. Subjects required three breaths to empty the VHC in 96% of the tests.
  
  
  CONCLUSIONS
  Actuating the pMDI into a small-volume nonelectrostatic VHC during exhalation reduced by 11% the amount of fluticasone captured at the exit of the VHC. Asthmatic children (5-8 years old) need three or less breaths to empty the small-volume VHC (NCT01714063).
authors.affiliation: 1 Pulmonology Section, Department of Pediatrics, UAMS/COM , Pediatric Aerosol Research Laboratory, Little Rock, Arkansas.
authors.forename: Ariel
authors.initials: A
authors.lastname: Berlinski
authors.affiliation: 2 Respironics, Inc. , a Philips Healthcare Company, Murrysville, Pennsylvania.
authors.forename: Dirk
authors.initials: D
authors.lastname: von Hollen
authors.affiliation: 3 Respironics Respiratory Drug Delivery (UK) Ltd , a Business of Philips Electronics UK Ltd, Chichester, United Kingdom .
authors.forename: Ross H M
authors.initials: RHM
authors.lastname: Hatley
authors.affiliation: 3 Respironics Respiratory Drug Delivery (UK) Ltd , a Business of Philips Electronics UK Ltd, Chichester, United Kingdom .
authors.forename: Lucy E A
authors.initials: LEA
authors.lastname: Hardaker
authors.affiliation: 4 InDevCo AB , Nyköping, Sweden .
authors.forename: Kurt
authors.initials: K
authors.lastname: Nikander
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D004867:Equipment Design; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage*; D006801:Humans; D036503:Inhalation Spacers; D008297:Male; D036501:Metered Dose Inhalers; D016037:Single-Blind Method; D013990:Tidal Volume
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D000068298:Fluticasone
keywords: asthma; breathing pattern; fluticasone propionate; inhalation technique; valved holding chamber