NONINVASIVE MEASUREMENT OF AIRWAY RESPONSIVENESS IN ALLERGIC MICE USING BAROMETRIC PLETHYSMOGRAPHY

To study the mechanisms and kinetics underlying the development of inc reased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric wholebody plethysmograp hy and increases in enhanced pause (Penh) as an index of airway obstru ction, we measured responses to inhaled methacholine in conscious, unr estrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measu red as Penh was associated with increased IgE production and eosinophi l lung infiltration. In a separate approach we confirmed the involveme nt of the lower airways in the response to aerosolized methacholine us ing tracheotomized mice. Increases in Penh values after methacholine c hallenge were also correlated with increased intrapleural pressure, me asured via an esophageal tube. Lastly, mice demonstrating AR using a n oninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta(2)-agon ist. These data indicate that measurement of AR to inhaled methacholin e by barometric whole-body plethysmography is a valid indicator of air way hyperresponsiveness after allergic sensitization in mice. The meas urement of AR in unrestrained, conscious animals provides new opportun ities to evaluate the mechanisms and kinetics underlying the developme nt and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.