PERSISTENT AIRWAY HYPERRESPONSIVENESS AND HISTOLOGIC ALTERATIONS AFTER CHRONIC ANTIGEN CHALLENGE IN CATS

We studied the effect of chronic immune sensitization on the airway re activity and associated cytologic and histologic alterations in initia lly nonatopic cats, a species that spontaneously develops idiopathic a sthma. Seven cats were sensitized by intramuscular injection of Ascari s suum antigen (AA) for 4 wk, and four other cats served as sham contr ols. Airway sensitization was demonstrated by an increased response to nebulized AA in sensitized animals (R(L) = 45.9 +/- 6.1 cm H2O/L/s, v ersus a baseline response of 24.7 +/- 1.5 cm H2O/L/s, p < 0.01), and h yperresponsiveness was demonstrated by an increased response to acetyl choline (ACh)-challenge 24 h after AA (similar to 1.0 log decrease in PD200, p < 0.01). The number of eosinophils in the sensitized animals' bronchoalveolar lavage (BAL) fluid increased 12-fold (p < 0.01 versus control) in response to AA challenge; 32 +/- 5% of the BAL eosinophil s had a specific density < 1.050, versus 8 +/- 2% prior to AA challeng e (p < 0.05). There was no change in airway reactivity, eosinophil rec overy, or density in the control group 24 h after sham challenge with saline. The same seven sensitized cats further received nebulized AA t hree times weekly for 4 to 6 wk, after which BAL samples were again ob tained and ACh dose-response curves generated 72 h after the final adm inistration of nebulized AA. Airway hyperresponsiveness increased (sim ilar to 1.5 log decrease in PD200, p < 0.001) and the number of eosino phils recovered in BAL fluid was increased 11-fold (p < 0.05). Necrops y specimens demonstrated bronchoconstriction in AA-challenged animals but not controls; luminal narrowing was accompanied by: (1) a 29.0 +/- 0.34% increase in smooth-muscle thickness (p < 0.05); (2) goblet-cell and submucosal-gland hypertrophy and hyperplasia; and (3) epithelial erosion and eosinophilic infiltration. We demonstrate in nonhuman spec ies persistent airway hyperreactivity associated with a complete const ellation of histologic changes in epithelium, smooth muscle, and mucus glands, and cytologic changes in BAL fluid, all induced by immune sen sitization. Our data suggest that chronic immune sensitization per se could be a salient factor in causing many of the changes associated wi th chronic bronchial asthma.