Modeling the acute- and late-phase responses to peripheral airway cooling and desiccation

Acute bronchoconstriction after isocapnic hyperpnea can be produced in most asthmatic individuals. However, the existence of a late-phase response is less certain. We used a canine model of isocapnic hyperpnea to test the hypothesis that this discrepancy is due to differences in the challenge threshold for the responses. Acute-phase and late-phase bronchoconstriction was measured in nine dogs after peripheral airway exposure to unconditioned air. Additionally, bronchoalveolar lavage fluid (BALF) was obtained during the late-phase response. The acute-phase response was a polynomial function with a decreasing slope at higher challenges, whereas the late-phase response suggested that a minimum threshold of challenge severity was needed to produce late-phase bronchoconstriction. BALF leukocyte and eicosanoid concentrations had linear relationships with challenge severity. Our data support the hypothesis that acute- and late-phase posthyperpnea responses have different dose-response relationships, a fact that may explain the frequent lack of a late-phase response. However, our data suggest that mild inflammation can be induced with relatively lower challenge severity.