title: Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer.
abstract: The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device. Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer, in a flow range relevant to schoolchildren. In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer was determined. Mean PIF was 104 L.min-1 and all children aged > 5 yrs performed a PIF > 60 L.min-1. Sixteen children aged 8-15 yrs with exercise-induced asthma (EIA) took part in the main trial comparing the protective effect of 12 micrograms formoterol inhaled at 60 and 120 L.min-1. The effect from high and low inspiratory flow was judged from the protective effect against EIA 12 h after drug administration. The decrease in forced expiratory volume in one second (FEV1) after exercise was 34% on the placebo day, but only 15% when formoterol was inhaled at the high flow rate. This difference was statistically significant. The decrease in FEV1 was 23% after treatment with formoterol inhaled at the low flow rate, that was not significantly different from placebo or from high-flow formoterol treatment. These clinical findings correspond with the in vitro findings of flow-dependent fine particle mass from the Aerolizer, and corroborate the relationship between fine particle mass of aerosol and clinical effect. The results indicate a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer, within the range of inspiratory flow rate obtainable by school-children. This questions its applicability in children with asthma.
authors.affiliation: Dept of Paediatrics, National University Hospital, Copenhagen, Denmark.
authors.forename: K G
authors.initials: KG
authors.lastname: Nielsen
authors.forename: M
authors.initials: M
authors.lastname: Skov
authors.forename: B
authors.initials: B
authors.lastname: Klug
authors.forename: M
authors.initials: M
authors.lastname: Ifversen
authors.forename: H
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D001250:Asthma, Exercise-Induced / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D011208:Powders; D012123:Pulmonary Ventilation / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D011208:Powders; D000068759:Formoterol Fumarate