Investigation Of Airway Mucus Rheological Behaviors In Asthma And Their Determinants And Clinical Implications

Airway mucus is an important defense barrier for airways and lung, which traps exogenous hazardous particulate matters and excludes them out of body via beating of the cilia and coughing, but selectively allows passage of beneficial matters. This precise defense function in normal physiological state largely relies on appropriate rheological properties of the airway mucus. In asthma, the patient’s mucus is highly viscous with abnormal rheological behaviors, which causes impaired flow of the mucus and in worse cases form mucus plug (sputum plug) to obstruct the airway or even threaten life. However, mechanisms of the rheological alteration in asthmatic airway mucus is not clear. Thus, through biomechanics and biorheology methods, we propose in regards of normal and asthmatic airway mucus to:1) Characterize and analyze mucus compositions (esp. mucin, inflammatory cells) and their changes;2) Systematically investigate bulk and micro-rheological behaviors and their determinants;3) Examine microscopic characteristics of the mucus in relation to its composition;4) Establish constitutive equations and corresponding numerical simulation method for mucus rheology;5) Reveal the influence of mucus rheology on transportation of particulate matters.We demonstrated that both the normal and asthmatic airway mucus exhibited soft-solid behavior that fitted well to classical Burgers Model. The asthmatic mucus exhibited a slight shear-thickening at low shear rate, then nonlinearly shear-thinning until the highest shear rate, while the simulated normal mucus exhibited nonlinearly shear-thinning consistently across all shear rates. The storage and loss moduli of the simulated mucus were comparable to those published in literature. The macroscopic rheological behaviors of the mucus were closely related to the microstructure formed due to aggregation and self-assembly.This study provides scientific basis for further understanding altered rheological behaviors of asthmatic airway mucus. These findings may be important to the pathological mechanisms as well as evaluation of drug delivery, may also provide related new ideas for clinical diagnosis and treatment for asthma.