Stepwise Changes In Lung Function And Growth With Age In Mice

Rationale: The lungs continue to grow postnatally until adulthood. This growth is reflected in longitudinal changes in lung function whereby lung function “improves” with age before peaking in early adulthood. Early postnatal life has been identified as a time when susceptibility to respiratory insults is high due to the rapid growth of the lung during this time. However, while age dependent changes in lung function are typically modelled as smooth curves when plotted against height (as a proxy for lung size), additional periods of rapid somatic growth occur between birth and adulthood; particularly during puberty. Changes in lung function and growth during periods of rapid adolescent growth are poorly characterised. We aimed to examine age dependent changes in lung function in healthy mice and to correlate these changes with lung structure.

Methods: 2, 4, 6 and 8 week old naïve C57BL/6 mice were assessed for somatic growth (weight and body length), lung mechanics and lung volume. Lung mechanics and lung volume were measured in anaesthetised, tracheostomised and mechanically ventilated mice using a modification of the forced oscillation technique and plethysmography respectively. The respiratory system impedance was partitioned into parameters representing the airway (airway resistance, R ) and tissue (tissue damping, G; tissue elastance, H; hysteresivity = G/H) aw mechanics. Lungs were fixed and structure was assessed histologically according to ATS/ERS guidelines.

Results: Lung volume increased with age while R , G and H decreased. Lung volume and R were linearly associated with body length aw aw in the 2 and 8 week old mice, however there was no relationship between R (p = 0.12) or lung volume (p = 0.165), and age in 4 and 6 aw week old mice despite substantial increases in body length. In contrast, both G (p < 0.001) and H (p < 0.001) decreased significantly between 4 and 6 weeks of age. Hysteresivity remained constant across ages.

Conclusions: The substantial change in tissue mechanics without a corresponding increase in lung volume during adolescence in mice suggests that this stage represents a time of rapid parenchymal restructuring. Such rapid growth may lead to increased susceptibility to respiratory insults.