B. Marchette

Changes in airway permeability and responsiveness after exposure to ozone

The purpose of this investigation was to examine the relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O3). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 microCi/ml of [3H]histamine. The rate of appearance of the [3H]histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O3 for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O3, increased airway responsiveness and airway permeability were observed 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O3 had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O3-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O3 may be related to concomitant changes in airway permeability to this agent.

Differences between inhaled and intravenous carbachol in detecting O3-induced airway effects ☆

The response of specific lung resistance (SRL) to inhalation of 5 and 10 mg/ml carbachol was compared with the response of SRL to intravenous infusion of 2 and 5 micrograms/kg carbachol before and after a 2-day exposure to 0.5 ppm ozone (O3) in eight conscious sheep. Airway reactivity was defined as the slope of the dose-response curve and airway sensitivity as the largest increase in SRL after carbachol challenge. O3 exposure did not alter mean airway reactivity or mean airway sensitivity as determined by inhalation challenge. In contrast, O3 exposure significantly increased mean airway reactivity by 34% (P less than 0.01) and mean airway sensitivity by 31% (P less than 0.01) as assessed by intravenous challenge. The failure of O3 exposure to enhance responsiveness to inhaled carbachol may have been related to decreased airway penetration of the aerosol, possibly due to mucus hypersecretion. However, O3 exposure may have had a direct effect on the airway smooth muscle, thereby explaining the increased response to infused carbachol.