Pulmonary Function Assessment in Mouse Models

Mouse models have become indispensable for investigating the mechanics and pathogenesis of human respiratory diseases. Assessing pulmonary function in these animals involves a suite of invasive and non-invasive techniques designed to quantify airway resistance, lung compliance, expiratory flows and volume changes under both basal conditions and provoked challenges. Non-invasive whole-body and head-out plethysmography allow repeated measurements in conscious mice by detecting chamber pressure variations during spontaneous breathing. Invasive methods, such as the forced oscillation technique and negative pressure-driven forced expiration, yield high-precision values for respiratory resistance, tissue damping, elastance and forced expiratory volumes but require tracheal access and anaesthesia. Recent refinements in imaging and mechanical modelling have improved sensitivity and reproducibility, enabling multiparametric evaluation of cellular, anatomical and functional responses in models of asthma, fibrosis, emphysema and acute lung injury. Such advances underpin translational studies of pharmacological interventions and environmental insults, offering a robust platform for longitudinal investigations of airway hyperresponsiveness, tissue remodelling and therapeutic efficacy.

Research from Nature Portfolio

Innovations in non-invasive imaging have introduced low-dose planar cinematic X-ray lung function (XLF), which captures dynamic changes in thoracic dimensions during breathing without restraining or intubating the mouse. XLF provides enhanced sensitivity over unrestrained plethysmography for detecting treatment effects in allergic airway inflammation and correlates anatomical deformations with functional deficits. Complementary work with an artificial lung model has clarified the dual contributions of airway resistance and gas conditioning (heating and humidification) to chamber pressure signals in whole-body plethysmography. By delineating these components, investigators have highlighted limitations in the accuracy of tidal volume measurements and the derivation of surrogate indices, such as the enhanced pause, thereby guiding more precise interpretation of breathing patterns in diverse disease contexts.

Pulmonary Function Assessment in Mouse Models publication trend

The graph below shows the total number of articles in pulmonary function assessment in mouse models across all publications each year (not limited to Nature Index journals).

Technical terms

Forced oscillation technique (FOT): An invasive method applying oscillatory pressure waves to measure respiratory resistance and compliance.

Whole-body plethysmography (WBP): A non-invasive chamber technique that infers breathing parameters from pressure fluctuations during spontaneous respiration.

Forced vital capacity (FVC): The total volume of air exhaled forcefully following a full inspiration.

Forced expiratory volume in 0.1 s (FEV0.1): The volume of air expelled in the first 0.1 seconds of a forced expiration.

Midexpiratory flow (EF50): The flow rate at which 50 per cent of FVC has been exhaled, used as a non-invasive marker of airflow limitation.

Airway hyperresponsiveness (AHR): An exaggerated constrictive response of the airways to pharmacological or allergenic stimuli.

Enhanced pause (Penh): A dimensionless index derived from plethysmography pressure signals, historically used as a surrogate for airway resistance.

References

1. Invasive and noninvasive methods for studying pulmonary function in mice. Respiratory Research (2007).
2. Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness. Respiratory Research (2010).
3. Plethysmography measurements of respiratory function in conscious unrestrained mice. The Journal of Physiological Sciences (2015).
4. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models. Scientific Reports (2016).
5. Forced expiration measurements in mouse models of obstructive and restrictive lung diseases. Respiratory Research (2017).
6. Evaluation of a mechanical lung model to test small animal whole body plethysmography. Scientific Reports (2021).
7. Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice. Respiratory Research (2005).
8. Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model. Respiratory Research (2022).