Mechanical determinants of airways hyperresponsiveness

Asthmatic individuals typically experience exaggerated decrements in their ability to breathe after receiving standardized doses of smooth muscle agonist, a phenomenon known as airways hyperresponsiveness (AHR). Breathing difficulties are caused by excessive narrowing of the pulmonary airways, which is instigated by shortening of the airway smooth muscle (ASM). Exactly why many asthmatic individuals are hyperresponsive, however, remains controversial because of the many varied mechanisms that could possibly be involved. Nevertheless, much of the understanding of AHR comes down to a matter of considering the spatial configuration of the components that make up the airway, and the static and dynamic physical forces these components experience. In this review, we consider these mechanical factors, which are conveniently subdivided into three groups involving (i) the active forces construing to narrow the airways, (ii) the mechanical loads against which these forces must work, and (iii) the geometric transformation of a given degree of ASM shortening into airway narrowing. Each of these groups of factors has potent potential to influence AHR. It is likely, however, that they operate together to produce the AHR characteristic of severe asthma.