title: An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children Under Six Years Old.
abstract: BACKGROUND
  Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol.
  
  
  METHODS
  The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT.
  
  
  RESULTS
  Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction.
  
  
  CONCLUSIONS
  A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Patricia
authors.initials: P
authors.lastname: Tang
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Sharon S Y
authors.initials: SS
authors.lastname: Leung
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Eleanor
authors.initials: E
authors.lastname: Hor
authors.affiliation: 2 Department of Mechanical Engineering, University of Alberta , Edmonton, Canada .
authors.forename: Conor A
authors.initials: CA
authors.lastname: Ruzycki
authors.affiliation: 2 Department of Mechanical Engineering, University of Alberta , Edmonton, Canada .
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Carrigy
authors.affiliation: 2 Department of Mechanical Engineering, University of Alberta , Edmonton, Canada .
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
authors.affiliation: 3 Department of Respiratory and Sleep Medicine, John Hunter Hospital , Newcastle, New South Wales, Australia .
authors.forename: John D
authors.initials: JD
authors.lastname: Brannan
authors.affiliation: 4 School of Paediatrics and Child Health, The University of Western Australia , Crawley, WA, Australia .
authors.forename: Sunalene
authors.initials: S
authors.lastname: Devadason
authors.affiliation: 5 Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital , Camperdown, New South Wales, Australia .
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Anderson
authors.affiliation: 6 Children's Health and Environment Program, Queensland Children's Medical Research Institute, University of Queensland , Royal Children's Hospital, Herston, QLD, Australia .
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Kevin
authors.initials: K
authors.lastname: Samnick
authors.affiliation: 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000367:Age Factors; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002675:Child, Preschool; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D007223:Infant; D008353:Mannitol / Q000008:administration & dosage* / Q000737:chemistry; D008953:Models, Anatomic; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D011208:Powders; D011237:Predictive Value of Tests; D012119:Respiration; D012137:Respiratory System / Q000254:growth & development / Q000503:physiopathology
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D011208:Powders; D008353:Mannitol
keywords: airway hyper-responsiveness; asthma; bronchial provocation testing; mannitol powder; pediatric