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Advancing Fibrosis Studies: The Impact of Repeated Lung Function Monitoring

Lung function testing (LFT) is crucial for diagnosing and monitoring chronic lung diseases like idiopathic pulmonary fibrosis (IPF). In animal studies, particularly with mice, LFT is often used as an endpoint, requiring multiple animals to assess disease progression. A recent study by Ropke et al (2024) challenges this approach by exploring the feasibility of conducting repeated LFTs on the same individual mouse, reducing the number of animals used in experiments and allowing for longitudinal disease monitoring.

Repetitive LFT Do Not Aggravate Lung Fibrosis

The study aimed to evaluate whether repetitive invasive lung function maneuvers could impact the progression of lung fibrosis in mice. Using the flexiVent system, the researchers performed up to four lung function assessments over 28 days in healthy mice and those with adenoviral transforming growth factor-beta (AdTGF-β1)-induced fibrosis. Results showed that the repeated tests were well tolerated and did not worsen lung fibrosis, suggesting this method can be used in preclinical research without influencing the disease model.

Minimizing impact on animals

To ensure the well-being of the mice during the repetitive LFTs, the researchers used an orotracheal cannulation technique without surgical exposure of the trachea, minimizing injury risks. The flexiVent system was calibrated for each test to account for variations in the mechanical properties of the tracheal cannula. The tests involved ventilation strategies, including the forced oscillation technique (FOT), which measured various lung parameters such as inspiratory capacity and tissue elastance.

The study showed that the mice tolerated the procedures well, with only minor and temporary reductions in body weight. These changes were not attributed to the lung function tests but rather to the anesthesia used during the procedures. Both healthy and fibrotic mice recovered quickly, and there was no evidence of inflammation or exacerbated fibrosis in the lung tissue after repeated tests.

Implications for Research and Ethics

This research is particularly relevant for the field of pulmonary fibrosis, where animal models are invaluable for studying disease mechanisms and potential treatments. Repeated LFTs in individual mice offer several advantages, including the ability to track disease progression over time in the same animal, which reduces the number of mice needed for experiments. By applying repeated tests, researchers can better understand lung mechanics and fibrosis development in a more efficient and ethically responsible manner, supporting the ethical framework of the 3R principle—Reduce, Refine, and Replace.

Conclusion

The findings from this study pave the way for more efficient and ethical pulmonary research. By showing that repetitive lung function maneuvers do not exacerbate lung fibrosis in mice, researchers can now use this technique to monitor disease progression over time, reducing animal use and improving the precision of experimental outcomes.

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