Noninvasive and Invasive Pulmonary Function in Mouse Models of Obstructive and Restrictive Respiratory Diseases

TLDR

Pulmonary function analysis is a key tool for evaluating mouse respiratory disease models, yet controversy persists over the validity of many tests and which variables best monitor specific disease models. This study sought to delineate the strengths and limitations of existing pulmonary function techniques across respiratory disease models and to identify variables common to humans and mice. The authors compared one noninvasive unrestrained plethysmography method with two invasive devices—a Buxco forced maneuver system and a SCIREQ forced oscillation technique—in well‑established models of asthma, emphysema, and pulmonary fibrosis. Invasive techniques accurately quantified parenchymal disease through changes in functional residual capacity, total lung capacity, vital capacity, and compliance, distinguished respiratory diseases, and should become standard, whereas noninvasive tests were less effective, and airflow obstruction appeared only in emphysema at baseline but could be induced in asthma with methacholine, correlating with increased respiratory resistance.

Abstract

Pulmonary function analysis is an important tool in the evaluation of mouse respiratory disease models, but much controversy still exists on the validity of some tests. Most commonly used pulmonary function variables of humans are not routinely applied in mice, and the question of which pulmonary function is optimal for the monitoring of a particular disease model remains largely unanswered. Our study aimed to delineate the potential and restrictions of existing pulmonary function techniques in different respiratory disease models, and to determine some common variables between humans and mice. A noninvasive (unrestrained plethysmography) and two invasive pulmonary function devices (forced maneuvers system from Buxco Research Systems [Wilmington, NC] and forced oscillation technique from SCIREQ [Montreal, PQ, Canada]) were evaluated in well-established models of asthma (protein and chemical induced): a model of elastase-induced pulmonary emphysema, and a model of bleomycin-induced pulmonary fibrosis. In contrast to noninvasive tests, both invasive techniques were efficacious for the quantification of parenchymal disease via changes in functional residual capacity, total lung capacity, vital capacity, and compliance of the respiratory system. Airflow obstruction and airflow limitation at baseline were only present in emphysema, but could be significantly induced after methacholine challenge in mice with asthma, which correlated best with an increase of respiratory resistance. Invasive pulmonary functions allow distinction between respiratory diseases in mice by clinically relevant variables, and should become standard in the functional evaluation of pathological disease models.