AIRWAY EDEMA POTENTIATES AIRWAY REACTIVITY

Thickening of the airway wall has been hypothesized to be one of the m echanisms contributing to airway hyperresponsiveness in asthma. If suc h thickening of the wall is internal to the airway smooth muscle or ot herwise causes a decrease in baseline airway caliber, it should also c ause exaggerated airway responsiveness. In the present study, we used high-resolution computed tomography to directly measure the changes in the caliber and wall thickness of conducting airways after aerosol hi stamine challenge before and after normal saline volume loading. On se parate days, five anesthetized dogs received either a baseline aerosol challenge of 3 mg/ml of histamine for five breaths or the same aeroso l challenge immediately after a 100 mL/kg bolus of normal saline infus ed over a 10-min period. Baseline aerosol histamine challenge decrease d airway area to 71 +/- 2% (SE) of the control value (P < 0.05). Intra venous administration of 100 mL/kg of normal saline increased wall are a by decreasing airway luminal area to 78 +/- 3% of the control value (P < 0.01), with no change in outer airway area. Aerosol histamine cha llenge superimposed on this engorgement with normal saline challenge f urther decreased airway luminal area to 54 +/- 3% of the control value (P < 0.01). Quantitative modeling indicated that the edema in the air way wall was mostly outside the smooth muscle and that the smooth musc le shortening with histamine was similar with and without edema. We co nclude that a moderate degree of acute airway wall thickening can lead to a potentiated constrictor response to histamine.