It is self-evident that acute narrowing of the asthmatic airway and shortening of the airway smooth muscle are inextricably linked. Nonetheless, it was many years ago that research on the asthmatic airway and research on the biophysics of airway smooth muscle (ASM) had a parting of the ways . The study of smooth muscle biophysics took on a life of its own and pursued a deeply reductionist agenda, one that became focused to a large extent on myosin II and regulation of the acto-myosin cycling rate. The study of airway biology pursued a reductionist agenda as well, but one that became focused less and less on contractile functions of muscle and instead emphasized immune responses, inflammatory cells and mediators, and, to the extent that smooth muscle remained of interest, that interest centered mainly on synthetic, proliferative and migratory functions [2-7]. Inflammatory remodeling of the airway wall was also recognized as being a key event in the asthmatic diathesis [7-17]. Computational models of ever increasing sophistication were formulated in order to better understand the impact of inflammatory remodeling processes upon ASM shortening and acute airway narrowing but, remarkably, the muscle compartment of these models remained at a relatively primitive level, being represented by nothing more than the classical relationship of active isometric force vs. muscle length [13,16,18-22]. As discussed below, this description is now considered to be problematic because the very existence of a well-defined static force-length relationship has of late been called into question, as has the classical notion that the muscle possesses a well-defined optimal length. Rather, other factors intrinsic to the muscle, especially muscle dynamics and mechanical plasticity, as well as unanticipated interactions between the muscle and its load, are now understood to be major factors affecting the ability of the muscle to narrow the airway [1,23-27].
The topics addressed in this review are intended to highlight recent discoveries that bring airway biology and smooth muscle biophysics into the same arena once again. The emphasis is biophysical properties of airway smooth muscle as they relate to excessive airway narrowing. This is appropriate because, in the end, if airway inflammation didn't cause airway narrowing, then asthma might be a tolerable disease (Julian Solway, personal communication). But asthma is not a tolerable disease. In order to understand the multifaceted problem of bronchospasm in asthma, therefore, an integrative understanding that brings together a diversity of factors will be essential.