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 (Scnn1b-TG) mice and of the effects of neutrophil elastase (NE) knockout on its progression. Lungs from wild-type (WT), NE(-/-), Scnn1b-TG, and Scnn1b-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 Scnn1b-TG compared to WT mice from 0 days (20.25±6.50 vs. 9.60±2.07, P<0.05), and this effect was attenuated in Scnn1b-TG/NE(-/-) mice (5.33±3.67, P<0.001). Airway wall area percentage (WA%) was increased in Scnn1b-TG mice compared to WT from 14 days onward (59.2±6.3% vs. 49.8±9.0%, P<0.001) but was similar in Scnn1b-TG/NE(-/-) compared to WT at 60 days (46.4±9.2% vs. 45.4±11.5%, P=0.97). Air proportion (Air%) and mean linear intercept (Lm) were persistently increased in Scnn1b-TG compared to WT from 5 days on (53.9±4.5% vs. 30.0±5.5% and 78.82±8.44µm vs. 65.66±4.15µm, respectively, P<0.001), whereas in Scnn1b-TG/NE(-/-) Air% and Lm were similar to WT from birth (27.7±5.5% vs.27.2±5.9%, P =0.92 and 61.48±9.20µm vs. 61.70±6.73µm, P=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 Scnn1b-TG mice, and that it may serve as a sensitive endpoint for preclinical studies of novel therapeutic interventions for muco-obstructive lung diseases.

• Zhu, L.
• Duerr, J.
• Zhou-Suckow, Z.
• Wagner, W. L.
• Weinheimer, O.
• Salomon, J. J.
• Leitz, D.
• Konietzke, P.
• Yu, H.
• Ackermann, M.
• Stiller, W.
• Kauczor, H. U.
• Mall, M. A.
• Wielpütz, M. O.