Possible role of collagen reorientation during airway remodeling on mucosal folding

Airway remodeling in patients with chronic asthma is characterized by thickening and structural change of airway walls. It has been demonstrated in previous theoretical models that changes in airway thickness can have an important mechanical effect, in particular, on the mucosal folding induced by smooth muscle contraction. In this paper, we examine the effect of collagen fiber orientation change on the mucosal folding. The airway is modeled as a two-layer cylindrical tube, with the submucosa (outer layer) represented as isotropic tissue and subepithelial collagen layer (inner layer) as fiber-reinforced anisotropic tissue. In order to follow the most recent advancement for modeling anisotropic material, we carry out computation under a reduced form of strain energy, as well as a form of strain energy compatible with linear theory in infinitesimal strains. We explore the effects of varying collagen density, strain-stiffening behavior of collagen fibers as well as the layer thickness change on the folding behavior. We demonstrate that collagen orientation change can have a significant impact on mucosal folding, including the critical pressure required to induce folding and the buckling mode. We demonstrate that proper collagen density combined with proper collagen orientation might be a strategy used by organisms to prevent low-mode buckling thus to prevent airway narrowing. Deviation from these balances caused by disease status will favor low-mode buckling. We also find that the two forms of strain energy give very similar results, and therefore, most important features of buckling behavior can still be captured by the reduced form. We conclude that anisotropic property of the subepithelial collagen layer may be an important component in airway remodeling.