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.

Intranasally administered L. rhamnosus GG prevents the development of cardinal features of birch pollen-induced allergic asthma in a strain-specific manner.

Asthma may be induced by chemical sensitisers, via mechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitro intracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using an in vivo model, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, in Trpa1 and Trpv1 knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficient Kit(Wsh) (/Wsh) mice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR.

After a recovery period of 14 days an intranasal (i.n.) challenge with 0.003% active chlorine (in ClO) or vehicle (distilled water, HO) was given, followed by assessment of the breathing frequency. One day later, pulmonary function, along with pulmonary inflammation was determined. Lung permeability was assessed by means of total broncho-alveolar lavage (BAL) protein content and plasma surfactant protein (SP)-D levels. In vivo micro-CT imaging revealed enlargement of the lungs and airways early after NA treatment, with a return to normal at day 14. When challenged i.n. with ClO, NA-pretreated mice immediately responded with a sensory irritant response. Twenty-four hours later, NA/ClO mice showed airway hyperreactivity (AHR), accompanied by a neutrophilic and eosinophilic inflammation. NA administration followed by ClO induced airway barrier impairment, as shown by increased BAL protein and plasma SP-D concentrations; histology revealed epithelial denudation. These data prove that NA-induced lung impairment renders the lungs of mice more sensitive to an airway challenge with ClO, confirming the hypothesis that incomplete barrier repair, followed by irritant exposure results in airway hypersensitivity.

No abstract