Nonlinear compliance modulates dynamic bronchoconstriction in a multiscale airway model.

Area of Science:

• * Respiratory mechanics
• * Airway smooth muscle physiology
• * Biomechanical modeling

Background:

• * Deep inspirations (DI) effectively dilate constricted airways in non-asthmatic individuals but not in those with asthma.
• * Previous studies show length fluctuations reduce airway smooth muscle force, yet transmural pressure oscillations in intact airways do not replicate this bronchodilation.
• * A paradox exists between observations in isolated cells/tissues and intact airways regarding DI's bronchodilatory effects.

Purpose of the Study:

• * To investigate the biomechanical factors governing airway smooth muscle (ASM) response to breathing maneuvers, particularly deep inspirations (DI).
• * To resolve the discrepancy between DI's effects on isolated ASM and intact airways.
• * To develop a biomechanical model of the intact airway incorporating extracellular matrix (ECM) properties and ASM force generation.

Main Methods:

• * Development of a novel biomechanical model of the intact airway.
• * Inclusion of collagen recruitment-induced strain-stiffening of the ECM.
• * Modeling of dynamic actomyosin-driven force generation by ASM cells.

Main Results:

• * The model confirms limited bronchodilation from transmural pressure (PTM) fluctuations at certain mean PTM levels, consistent with intact airway studies.
• * Model predictions indicate greater bronchodilation is achievable when the airway is moved to a more compliant state on its pressure-radius curve before applying pressure fluctuations.
• * A nonlinear relationship between effective airway stiffness and PTM was identified, influenced by ECM strain-stiffening and ASM force, which is further modified by contractile agonists.

Conclusions:

• * The study hypothesizes that the degree of static airway compliance at the mean transmural pressure (PTM) dictates the maximum potential for bronchodilation.
• * Reduced mean PTM may enhance bronchodilation by increasing airway compliance.
• * Further experimental protocols are proposed to validate the model's predictions regarding airway compliance and bronchodilation.