In Vivo Measurements of Changes in Respiratory Mechanics with Age in Mice Deficient in Surfactant Protein D

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Abstract
Mice deficient in surfactant protein D [SP-D (−/−)] develop progressive emphysema with age, associated with loss of parenchymal tissue, subpleural fibrosis, and accumulation of abnormal elastin fibers. We measured the changes in lung function, partitioned into components for the airways and lung parenchyma, occurring with age in SP-D (−/−) mice at three ages (n = 8 per group) (5, 8, and 13 wk). Impedance spectra between 0.25 and 19.625 Hz were calculated and a model, consisting of an airway compartment [airway resistance (Raw) and inertance (Iaw)] and a constant-phase tissue compartment [coefficients of tissue damping (G) and elastance (H)], was fitted to the data. Hysteresivity was calculated as G/H. Adult values of Raw, G, and H are reached by 8 wk of age in wild-type controls. Raw and H were lower at all ages in SP-D (−/−) compared with the wild-type controls (p = 0.006 and 0.029, respectively), and a similar trend was seen in G (p = 0.060). The patterns of change in respiratory mechanics were similar in both SP-D (+/+) and (−/−) groups. There were no changes in hysteresivity with age and no differences between wild-type and SP-D (−/−) mice. These data demonstrate that the changes in lung structure in SP-D (−/−) mice are reflected in the mechanical properties of both airway and lung parenchyma measured in vivo.