Distinct long-term effects on lung function and airway remodeling in ovalbumin and house dust mite mouse models of experimental asthma.

Abstract

Although mouse models of acute allergic inflammation (AAI) have long been used to study asthma mechanisms, their ability to reproduce human disease remains controversial and long-term studies of chronic asthma remain scarce. We compared lung function and tissue changes in three experimental asthma models after four months of recovery. Using x-ray-based lung function (XLF) analysis, we assessed lung parameters and diaphragm motion, alongside lung expression of α-smooth muscle actin and key extracellular matrix proteins, collagen and elastin. A severe ovalbumin (OVA) model (SAA) produced stronger acute and long-term effects than a milder OVA model (MAA), reflected in both lung dysfunction and tissue remodeling. Lung function remained impaired in SAA and in a house dust mite (HDM) model months after recovery. However, SAA and HDM showed distinct long-term remodeling: While SAA revealed reduced decay rate, collagen deposition and elastin reduction, HDM induced no histological abnormalities but resulted in smaller lung areas and greater diaphragm motion. This first direct comparison of long-term outcomes across AAI models highlights substantial heterogeneity that parallels differences seen in human asthma. These findings underscore the need for careful model selection in studies of chronic asthma and demonstrate the sensitivity of non-invasive XLF for detecting subtle changes.