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

The response of specific lung resistance (SR_L) to inhalation of 5 and 10 mg/ml carbachol was compared with the response of SR_L to intravenous infusion of 2 and 5 μg/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 SR_L 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 < 0.01) and mean airway sensitivity by 31% (P < 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.