µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice.

Muco-obstructive lung diseases are characterized by airway obstruction and hyperinflation, which can be quantified by imaging. Our aim was to evaluate µCT for longitudinal quantification of muco-obstructive lung disease in β-epithelial Na channel overexpressing (-TG) mice and of the effects of neutrophil elastase (NE) knockout on its progression. Lungs from wild-type (WT), NE, -TG, and -TG/NE mice were scanned with 9-µm resolution at 0, 5, 14, and 60 days of age, and airway and parenchymal disease was quantified. Mucus adhesion lesions (MAL) were persistently increased in -TG compared with WT mice from 0 days (20.25 ± 6.50 vs. 9.60 ± 2.07, < 0.05), and this effect was attenuated in -TG/NE mice (5.33 ± 3.67, < 0.001). Airway wall area percentage (WA%) was increased in -TG mice compared with WT from 14 days onward (59.2 ± 6.3% vs. 49.8 ± 9.0%, < 0.001) but was similar in -TG/NE compared with WT at 60 days (46.4 ± 9.2% vs. 45.4 ± 11.5%, = 0.97). Air proportion (Air%) and mean linear intercept () were persistently increased in -TG compared with WT from 5 days on (53.9 ± 4.5% vs. 30.0 ± 5.5% and 78.82 ± 8.44 µm vs. 65.66 ± 4.15 µm, respectively, < 0.001), whereas in -TG/NE, Air% and were similar to WT from birth (27.7 ± 5.5% vs. 27.2 ± 5.9%, = 0.92 and 61.48 ± 9.20 µm vs. 61.70 ± 6.73 µm, = 0.93, respectively). Our results suggest that µCT is sensitive to detect the onset and progression of muco-obstructive lung disease and effects of genetic deletion of NE on morphology of airways and lung parenchyma in -TG mice, and that it may serve as a sensitive endpoint for preclinical studies of novel therapeutic interventions for muco-obstructive lung diseases.