RELATIONSHIPS AMONG ALLERGEN-INDUCED EARLY AND LATE-PHASE AIRWAY OBSTRUCTIONS, BRONCHIAL HYPERREACTIVITY, AND INFLAMMATION IN CONSCIOUS, UNRESTRAINED GUINEA-PIGS

The relationships among allergen-induced early asthmatic reactions (EA Rs) and late asthmatic reactions (LARs), early (between EAR and LAR) a nd lace (after LAR) changes in bronchial reactivity to histamine and i nfiltration of inflammatory cells into the airways were investigated w ith a new model of chronically instrumented, unrestrained, and ovalbum in-sensitized guinea pigs. Two different provocation strategies were e xamined. With the use of stepwise increasing allergen concentrations, all 21 animals responded with an EAR, which in 15 animals (71%) was fo llowed by an LAR. By inhalation of a single allergen concentration for up to 15 minutes, II of 14 animals showed an EAR, which in 10 animals (71%) was followed by an LAR One animal did not respond, whereas the remaining two showed only an LAR. At 6 hours (after the EAR) and 24 ho urs (after the LAR) after allergen provocation, a significant bronchia l hyperreactivity (BHR) toward histamine aerosol was observed in the d ual responding animals (both protocols), but no significant changes we re observed in animals with a single EAR or a single LAR. Significant correlations were found between the initial increase in airway obstruc tion after allergen provocation and the severity of the EAR and LAR as well as the early and late BHR; in addition, a significant correlatio n was found between the early and late BHR. In contrast, the severity of the LAR did not correlate with the BHR at 6 hours and 24 hoots. At 6 hours, there was a marked tendency to an increase in the number of e osinophils and a significant increase in the number of neutrophils in the bronchoalveolar lavage. At 24 hours after provocation, the number of eosinophils and neutrophils was significantly enhanced. These data suggest that early activation of mast cells and/or inflammatory leukoc ytes may determine the development of the LAR, as well as the early an d late BHR, although there appears to be no causal relationship betwee n the BHR at both time points and the severity of the LAR. The relatio nships among allergen-induced EAR and LAR, early and late BHR and airw ay inflammation observed in the new guinea pig model are strikingly si milar to those observed in. patients with asthma.