Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs.
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.
Stevens
W H
WH
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
Adelroth
E
E
Wattie
J
J
Woolley
M J
MJ
Ellis
R
R
Dahlbäck
M
M
O'Byrne
P M
PM
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*
D000336:Aerosols; D011282:Pregnenediones; D019819:Budesonide; D010126:Ozone; D007785:Lactose; D000109:Acetylcholine