Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice

OBJECTIVES: To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. DESIGN: Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. INTERVENTIONS: For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. RESULTS: Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). CONCLUSIONS: Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.