The development of bronchial hyperresponsiveness to cholinergic agents in relation to antigen sensitization and repeated antigen challenge was investigated in a rabbit model. Rabbits immunized to produce preferentially specific IgE antibodies had a modest enhancement of their bronchoconstrictive response (measured as an increase in pulmonary resistance) to aerosolized methacholine compared to sham-immunized and unimmunized controls. A further enhancement was observed subsequent to a series of seven antigen challenges given transtracheally, such that the geometric mean dose of methacholine required to increase pulmonary resistance by 100% (PD 100 RL) was 89 cumulative breath units (CBU) compared to 372 CBU for sham-immunized controls and 871 CBU for unimmunized controls (p < 0.05 for ANOVA). Although methacholine also decreased dynamic compliance, the changes were not different among the three groups. Isolated intrapulmonary bronchi from the three groups did not differ in log concentration of methacholine yielding a half-maximal contraction (log EC50). The range of EC50 values was 15-fold compared to a 90-fold range of PD100 RL. In vivo cholinergic responsiveness of the pupillary muscle did not correlate with bronchial responsiveness. Thus, pulmonary antigen challenge of IgE-producing rabbits produced a marked increase in bronchial responsiveness which did not correlate with in-vitro bronchial responsiveness or with in vivo pupillary responsiveness.
- Pulmonary resistance
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