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.