title: Extra-fine particles improve lung delivery of inhaled steroids in infants: a study in an upper airway model.
abstract: BACKGROUND
  The particles of a new hydrofluoroalkane-134a (HFA)-beclomethasone dipropionate (BDP) metered-dose inhaler (Qvar; 3M Pharmaceuticals; St. Paul, MN) are considerably smaller than those of chlorofluorocarbon (CFC)-BDP. This may improve lung deposition in infants who inhale nasally and have irregular breathing patterns and small airways.
  
  
  OBJECTIVE
  To compare the dose delivered to the lungs of HFA-BDP and CFC-BDP at different breathing patterns using an upper airway model of an infant.
  
  
  METHODS
  An anatomically correct upper airway model of a 9-month-old child with an open nasal airway was connected to an impactor and breathing simulator. HFA-BDP, 100 microg, and CFC-BDP, 100 micro g, were delivered to the model through a detergent-coated, small-volume spacer. The total dose leaving the model (lung dose), its particle size distribution, and median mass aerodynamic diameter (MMAD) were assessed during simulated tidal breathing with tidal volumes (VTs) of 50 mL, 100 mL, and 200 mL, and 30 breaths/min. Dose was expressed as percentage of nominal dose.
  
  
  RESULTS
  Lung doses for HFA-BDP were 25.4%, 26.5%, and 30.7% compared with 6.8%, 4.8%, and 2.1% for CFC-BDP at VTs of 50 mL, 100 mL, and 200 mL, respectively. The dose of particles < 2.1 microm to the lung for HFA-BDP was 23 to 28% compared with 0.6 to 0.8% for CFC-BDP. The lung dose of CFC-BDP mainly consisted of particles between 2.1 microm and 4.7 microm. MMAD for HFA-BDP was 1.2 microm, and 2.6 to 3.3 microm for CFC-BDP depending on VT. The lung dose for CFC-BDP decreased significantly with increasing VT. HFA-BDP lung dose did not alter significantly with VT.
  
  
  CONCLUSIONS
  In this infant model study, the use of HFA-BDP with a high dose of particles < 2.1 microm improves the dose delivered to the lungs substantially. Furthermore, the large proportion of extra-fine particles in HFA-BDP results in lung doses less dependent on breathing pattern compared with CFC-BDP.
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, Sophia Childrens Hospital/Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Hettie M
authors.initials: HM
authors.lastname: Janssens
authors.forename: Johan C
authors.initials: JC
authors.lastname: De Jongste
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Harm A W M
authors.initials: HA
authors.lastname: Tiddens
mesh_terms: D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000008:administration & dosage*; D001507:Beclomethasone / Q000008:administration & dosage; D017402:Chlorofluorocarbons / Q000008:administration & dosage; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D007223:Infant; D008168:Lung / Q000378:metabolism*; D036501:Metered Dose Inhalers; D008953:Models, Anatomic; D010316:Particle Size; D013256:Steroids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D001507:Beclomethasone; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; D013256:Steroids; C094049:apaflurane; D005466:Fluorocarbons