In the present report, we show that the enhanced pause (Penh), a novel
indicator of airway responsiveness to
bronchoconstrictors, can also be a good marker of airway response to an
allergen challenge in a murine model of
asthma. Male BALB/c mice were sensitized with
ovalbumin (OVA) through a combination of
intraperitoneal injection and
aerosol inhalation. After this immunization, the OVA-specific
IgE titer in serum increased to a significantly higher level than in a saline/PBS-treated control group. After the final OVA
aerosol challenge, Penh was repeatedly measured in conscious, unrestrained mice, according to the time schedule. Penh increased gradually after the challenge and reached a maximal value at 24 hours that was significantly higher than the control value (p < 0.01). Histologic examination of the lung revealed airway
inflammation with an invasion by eosinophils and lymphocytes from vessels into the peribronchial interstitium and the mucosal and submucosal areas of the bronchus. There was a strong correlation between the Penh value and eosinophil number in bronchoalveolar lavage fluid (r = 0.699, p < 0.0001). Moreover, Penh also correlated strongly with the intensity score of histologic findings. These results suggest that the bronchial response to a specific
allergen could be followed in a particular individual through the noninvasive Penh method, and that Penh accurately reflects the intensity of eosinophilic bronchial
inflammation. This system would be applicable to a noninvasive, chronological evaluation of various experimental interventions in a murine model of
asthma.