Fibrotic and Emphysematous Murine Lung Mechanics Under Negative-Pressure Ventilation.

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and the progressive nature heightens the calamity of the disease. Despite countless existing COPD studies, lung mechanics are often reported under positive-pressure ventilation (PPV) and implications and extrapolations made from these studies pose serious restrictions as recent works have divulged disparate elastic and energetic results between PPV and more physiological negative-pressure counterparts (NPV). This non-equivalence of PPV and NPV needs to 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 elastase-induced emphysema and dust-induced fibrosis models under positive- and negative-pressure and exploring biomarker resolution. We find that, for emphysema, under NPV, volume, compliance (C, C_start, C_def), and hysteresis are increased in diseased states and that under PPV only compliance (C, C_start) is increased. For fibrosis, under NPV, volume, compliance (C, C_inf, C_def, K), and hysteresis are decreased whereas under PPV only volume and static compliance decreased. These significances were observed solely at higher pressures (40 cmH₂O). 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 emphysema and fibrosis compared to PPV counterparts, suggesting the resolution of biomarkers when applied under NPV research considerations may offer greater versatility.