Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography

TLDR

Animal models are essential for studying the mechanisms and kinetics of increased airway responsiveness after allergic sensitization. The study aims to evaluate airway hyperresponsiveness mechanisms and therapeutic interventions using non‑restrained, conscious mice. Barometric whole‑body plethysmography was used to measure Penh responses to inhaled methacholine in conscious, unrestrained mice, with additional confirmation via tracheotomized mice and esophageal pressure monitoring. Sensitized mice exhibited heightened Penh responses to methacholine, correlated with IgE, eosinophilic infiltration, and intrapleural pressure, and these responses were reduced by β2‑agonist, confirming that plethysmography accurately reflects airway hyperresponsiveness.

Abstract

To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained 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 measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive 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 β2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.