title: Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs.
abstract: Inhaled corticosteroids are known to reduce components of the airway inflammation characteristic of asthma and improve airway hyperresponsiveness. However, the effect of inhaled corticosteroids on ozone-induced airway responses is unknown. Eight dogs inhaled budesonide [2.74 +/- 0.25 (SE) mg/day] or lactose powder twice daily for 7 days before inhaling ozone (3 ppm for 30 min) or dry air. Acetylcholine airway responsiveness was measured before and 1 h after ozone, followed by a bronchoalveolar lavage (BAL). The response to acetylcholine was expressed as the concentration causing an increase in lung resistance of 5 cmH2O.l-1.s above baseline (acetylcholine provocation concentration). Budesonide pretreatment significantly attenuated the ozone-induced increase in pulmonary resistance (P = 0.003) and neutrophil influx into BAL (P = 0.001) and significantly reduced BAL eosinophils (P = 0.026). However, budesonide pretreatment had no significant effect on ozone-induced airway hyperresponsiveness. After budesonide, the acetylcholine provocative concentration fell from 5.96 mg/ml (%SE 1.46) before to 1.11 mg/ml (%SE 1.63) after ozone (P = 0.006). After lactose, the acetylcholine provocative concentration fell from 5.34 mg/ml (%SE 1.40) before to 0.50 mg/ml (%SE 1.85) after ozone (P = 0.001). Dry air inhalation did not cause airway hyperresponsiveness (P = 0.68). These results suggest that ozone-induced airway hyperresponsiveness is steroid resistant and that airway neutrophils or eosinophils are not important in its pathogenesis.
authors.affiliation: Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
authors.forename: W H
authors.initials: WH
authors.lastname: Stevens
authors.forename: E
authors.initials: E
authors.lastname: Adelroth
authors.forename: J
authors.initials: J
authors.lastname: Wattie
authors.forename: M J
authors.initials: MJ
authors.lastname: Woolley
authors.forename: R
authors.initials: R
authors.lastname: Ellis
authors.forename: M
authors.initials: M
authors.lastname: Dahlbäck
authors.forename: P M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D019819:Budesonide; D002465:Cell Movement / Q000187:drug effects; D004285:Dogs; D007785:Lactose / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D010126:Ozone; D011282:Pregnenediones / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000503:physiopathology*
chemical_list: D000336:Aerosols; D011282:Pregnenediones; D019819:Budesonide; D010126:Ozone; D007785:Lactose; D000109:Acetylcholine