Forced expiration measurements in mouse models of obstructive and restrictive lung diseases

Abstract

BackgroundPulmonary function measurements are important when studying respiratory disease models. Both resistance and compliance have been used to assess lung function in mice. Yet, it is not always clear how these parameters relate to forced expiration (FE)-related parameters, most commonly used in humans. We aimed to characterize FE measurements in four well-established mouse models of lung diseases.MethodDetailed respiratory mechanics and FE measurements were assessed concurrently in Balb/c mice, using the forced oscillation and negative pressure-driven forced expiration techniques, respectively. Measurements were performed at baseline and following increasing methacholine challenges in control Balb/c mice as well as in four disease models: bleomycin-induced fibrosis, elastase-induced emphysema, LPS-induced acute lung injury and house dust mite-induced asthma.ResultsRespiratory mechanics parameters (airway resistance, tissue damping and tissue elastance) confirmed disease-specific phenotypes either at baseline or following methacholine challenge. Similarly, lung function defects could be detected in each disease model by at least one FE-related parameter (FEV0.1, FEF0.1, FVC, FEV0.1/FVC ratio and PEF) at baseline or during the methacholine provocation assay.ConclusionsFE-derived outcomes in four mouse disease models behaved similarly to changes found in human spirometry. Routine combined lung function assessments could increase the translational utility of mouse models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0610-1) contains supplementary material, which is available to authorized users.

Low‐dose administration of bleomycin leads to early alterations in lung mechanics

“…and i.p . BLM treatment (De Langhe et al., ; Devos et al., ; Li et al., ). Interestingly, we report changes in A , an estimate of inspiratory capacity, as early as day 7 of BLM treatment.…”

Perinatal nicotine with or without early life influenza infection leads to lung dysfunction with age.

“…LPS leads to TLR signaling in the lungs, which leads to inflammation, immune cell infiltration (neutrophils, macrophages, and CD4 + T cells), and increases MMP-9/12 (113). In these models, LPS causes enlarged air spaces, thickening of alveolar walls, and lung functional abnormalities (increased airway resistance and decreased PEF) consistent to what is seen in humans (113,114).…”

“…Interestingly, animals exposed chronically to nicotine also showed decreased Newtonian resistance, a parameter considered to represent resistance of the large airways (114). The latter is not common in patients with tobacco smoke-related COPD or in animal models of emphysema, which typically show increased airway resistance (114). It is conceivable that this is related to the observed increase in collagen around the airways, which could theoretically make the airways rigid, thereby 'stenting' the airways open.…”

“…This model is achieved through intratracheal or aerosol inhalation of elastolytic enzymes such as porcine pancreatic elastase, human neutrophilic elastase, and papain. This model leads to alveolar septa destruction and results in lung functional abnormalities (increased airway resistance, decreased tissue elastance, decreased tissue damping, increased IC, increased FVC, and decreased PEF) as seen in humans (113,114). Inducing chronic bronchiolitis in animals is most commonly conducted through intranasal or aerosolized inhalation of lipopolysaccharide (LPS) (111,113,114).…”

“…This model leads to alveolar septa destruction and results in lung functional abnormalities (increased airway resistance, decreased tissue elastance, decreased tissue damping, increased IC, increased FVC, and decreased PEF) as seen in humans (113,114). Inducing chronic bronchiolitis in animals is most commonly conducted through intranasal or aerosolized inhalation of lipopolysaccharide (LPS) (111,113,114). LPS leads to TLR signaling in the lungs, which leads to inflammation, immune cell infiltration (neutrophils, macrophages, and CD4 + T cells), and increases MMP-9/12 (113).…”