New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma.
We revisit the airway wall model of Lambert et. al. (Lambert RK, Wiggs BR, Kuwano K, Hogg JC, and Pare PD. J Appl Physiol 74: 2771-2781, 1993). We examine in detail the notion of a general airway bistability such that the airway lumen can suddenly decrease from a relatively open to a relatively closed condition without needing additional increase in active airway smooth muscle (ASM) tension during the stimulation. The onset of this bistability is an emergent consequence of the balance of forces associated with airway wall properties, parenchymal tissue properties, maximum lung elastic recoil, and the maximum stress that the ASM can generate. In healthy lungs, we find that all these properties reside in conditions that largely prevent the emergence of the bistability even during maximum ASM stimulation. In asthmatic airways, however, the airway wall and ASM remodeling conditions can tip the balance so as to promote the onset of the bistability at a lower dose of ASM stimulation (enhanced sensitivity) and then work to amplify the maximum constriction reached by each airway (enhanced reactivity). Hence, a larger fraction of asthmatic airways can display overall airway hyperreactivity. Simulations studies examine the role of increasing ASM maximum tension, airway wall stiffening, reduced lung volume, and decreased parenchymal tethering. Results predict that the single most important factor causing this airway hyperreactivity is amplified maximum ASM tension and not a thickening of the airway wall per se.
Affonce
Derek A
DA
Biomedical Engineering Department, Boston University, 44 Cummington St., Boston, MA 02215, USA. daffonce@bu.edu
Lutchen
Kenneth R
KR
D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D003198:Computer Simulation; D004548:Elasticity; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D009130:Muscle, Smooth / Q000503:physiopathology*; D033081:Shear Strength; D013314:Stress, Mechanical