Heterogeneous distribution of mechanical stress in human lung: A mathematical approach to evaluate abnormal remodeling in IPF

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. A recently proposed pathogenic model suggests that the concurrent action of cell senescence, exposure to cigarette smoke and mechanical stress due to respiratory lung movements lead to a localized exhaustion of tissue renewal capacity with eventual alveolar loss and abnormal lung remodeling. In this study we have compared the distribution of IPF lesions, as shown by TC radiological images, with the hypothetical distribution of maximal mechanical stress obtained by a simplified mathematical model. The geometry and distribution of stress as determined by our simulation are closely similar to those demonstrated in vivo in the lungs of patients with idiopathic pulmonary fibrosis using high resolution CT scan radiological imaging. These data argue in favor of the recently proposed contribution of mechanical stress to progressive damage and remodeling of lung parenchyma in IPF. The parameters of the model can be tuned on the age of the patients.