The effect of ozone on reactivity of upper and lower airways in guinea-pigs

1. The effect of ozone inhalation on the responsiveness of upper and lower airways to histamine was examined in guinea-pigs. 2. The exposure of conscious guinea-pigs to 3.5 p.p.m. ozone for 30 min rendered their lower airways 2-3 fold more sensitive to the bronchoconstrictor action of i.v. histamine, as assessed subsequently under anaesthesia. 3. The development of lower airway hyperreactivity was not modified by bilateral cervical vagotomy or pretreatment with BW 755C, FPL 55712 or SC-39070. 4. Under the conditions used, ozone exposure produced a mild inflammatory response as monitored by bronchoalveolar lavage, characterized by epithelial damage and prostaglandin E2 generation, but no cellular infiltration or oedema. 5. In contrast to the lower airways, upper airway resistance was reduced by i.v. histamine. This response was not affected by ozone exposure. 6. Isolated tracheal preparations taken from ozone-exposed guinea-pigs were not significantly more sensitive to histamine than control tissues. 7. The mechanism of hyperreactivity in this model is unknown but does not depend on leukotriene generation or a vagal reflex.