Novel murine partial tracheal occlusion model with altered respiratory dynamics

The respiratory system is integrated to optimize efficiency. Dysfunction of one element often impacts others. For example, in chronic obstructive pulmonary disease (COPD), both obstructive sleep apnea and small airways dysfunction are associated with worse emphysema. In bronchopulmonary dysplasia (BPD), cystic lung disease and tracheobronchomalacia are often comorbid. Furthermore, childhood asthma predisposes to COPD. Although mouse models have elucidated key mechanisms in respiratory disease, to date, no models have accounted for how conducting airway dysfunction impacts alveolar structure and function. We report a novel murine partial tracheal occlusion (PTO) model and a complementary esophageal pressure monitoring technique to begin answering these questions. A 50% reduction in trachea diameter was achieved using a 19-gauge needle to prevent complete closure of a microsurgical clip on the anterior trachea. Esophageal pressure was measured by advancing a 3.5-French pressure transducing catheter 3 cm into the esophagus. In 8-10-wk-old C57BL/6 mice, PTO did not cause appreciable alteration of distal lung structure despite a 10-mmHg increase in transpulmonary pressure gradient. However, PTO after tracheal aspiration of 0.5 units of porcine pancreatic elastase (PPE) resulted in 20 µm greater (<i>P</i> < 0.001) mean linear intercept than PPE + sham. This model can be leveraged in mouse models of asthma, BPD, and COPD to understand how conducting airway dysfunction and increased transpulmonary pressure impacts distal lung structure. The PTO model is a relatively simple, well-tolerated model of conducting airway dysfunction that potentiates distal lung injury and expands our understanding of how mechanical forces influence pathological remodeling processes in the distal lung.<b>NEW & NOTEWORTHY</b> Lung diseases often involve both the conducting airways and the lung parenchyma, but we do not have tools to determine the mechanisms by which one affects the other. We developed a mouse partial tracheal occlusion model that increases the pressure required to generate a breath and also a novel way to measure this pressure. We can now test different hypotheses about how lung strain causes pathological lung remodeling.