Fibrotic and emphysematous murine lung mechanics under negative-pressure ventilation

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and the progressive nature heightens the calamity of the disease. In existing COPD studies, lung mechanics are often reported under positive-pressure ventilation (PPV) and extrapolations made from these studies pose restrictions as recent works have divulged disparate elastic and energetic results between PPV and more physiological negative-pressure ventilation (NPV) counterparts. This nonequivalence of PPV and NPV must be investigated under diseased states to augment our understanding of disease mechanics. To assess the comparability of diseased pulmonary mechanics in PPV and NPV, we pose a novel study to parse out the currently entangled contributions of ventilation mode and diseased state by analyzing murine PV curves from porcine pancreatic elastase (PPE) and hog dust extract (HDE) induced COPD models under positive and negative pressures. We find that, for PPE-exposed, under NPV, volume, compliance (C, C_start, and C_def), and hysteresis are increased in diseased states and that under PPV, only compliance (C and C_start) is increased. For HDE-exposed, under NPV, volume, compliance (C, C_inf, C_def, and K), and hysteresis are decreased, whereas, under PPV, only volume and static compliance decreased. All significant mechanical variations due to disease were observed solely at higher pressures (40 cmH₂O) under both PPV and NPV. Our nuanced conclusions indicate the detection capabilities of multiple mechanics-based biomarkers are sensitive to the ventilation mode, where NPV exhibits more altered mechanics metrics in PPE-exposed and HDE-exposed groups compared with PPV counterparts, suggesting the resolution of biomarkers when applied under NPV research considerations may offer greater versatility.NEW & NOTEWORTHY We evaluate whether ubiquitous pressure-volume (PV) curve biomarkers depend on the ventilation mode under which they were collected (i.e., positive- or negative-pressure ventilation). This is a significant investigation considering recent works have revealed PV curves are distinct and noninterchangeable under the two ventilation modes. Multiple biomarkers noted under negative-pressure ventilation are lacking from positive-pressure counterparts, albeit for small-scale species considerations. Future investigations should confirm the applicability of these findings for large-scale specimens for clinical considerations.