Head-Out Spirometry Accurately Monitors the Course of Pseudomonas aeruginosa Lung Infection in Mice

Abstract

Background: Classic infection models in rodents use lethal doses of bacteria as inocula, thus creating models which are rarely comparable to the clinical situation. Moreover, single time-point evaluation requires killing of the animals, necessitating large numbers of animals. Longitudinal parameters such as temperature appear to have a relatively low accuracy. Spirometry might be an accurate method to assess the course of a bacterial lung infection without the necessity to sacrifice the animals. Objectives: We measured lung function in C57BL/6JZtm mice following intratracheal infection with Pseudomonas aeruginosa and compared it to physiological parameters and lung histology. Methods: Head-out spirometry measuring 14 parameters was performed on C57BL6/J mice for eight days following a P. aeruginosa lung infection. Additionally rectal temperature, body weight and condition were assessed together with histological data and bacteriological clearance. Results: Several spirometric parameters were significantly altered for more than 72 h after inoculation, which was four times longer than observed alterations in physiological parameters such as temperature. Volume (amount of air inspired) decreased more than seven-fold within 6 h after inoculation and required 72 h to recover, rendering it the most sensitive spirometric parameter investigated. Spirometric and histological data correlated well. Conclusions: Our findings suggest that non-invasive head-out spirometry is a reliable and highly sensitive method to longitudinally assess the course of bacterial lung infections.