The Contractile Properties of Airway Smooth Muscle: How their Defects can be Linked to Asthmatic Airway Hyperresponsiveness?

Abstract

Asthma is a prevalent and sometimes debilitating lung disorder caused by diverse triggers in susceptible individuals. Based on the salutary effect of drugs relaxing airway smooth muscle (ASM) in the treatment of asthma, there is no doubt that airway narrowing elicited by ASM shortening is involved in the development of symptoms. Asthmatic individuals are also commonly hyperresponsive to stimuli acting directly on ASM, such as methacholine; especially when they are not treated optimally. This feature is called airway hypperresponsiveness (AHR) and is thought to contribute importantly to asthma symptoms. This is because the airway response measured in an experimental setting, such as during a methacholine challenge, is a good surrogate of the airway response that would occur in vivo in response to contractile agonists generated endogenously (e.g., leukotriene and histamine) following exposure to asthma triggers. Many muscle and non-muscle factors, as well as their interaction, can contribute to AHR. The present review focuses exclusively on muscle factors. It is important to understand that many contractile properties of ASM may allow narrowing of airways in vivo. These include force, amount and velocity of shortening, stiffness, ability to relax, and ability to tolerate and recover from oscillating stress caused by breathing maneuvers. It is also important to understand that the contractile capacity of ASM can vary in time and in response to external cues (ASM is adaptable). Any permanent and transient defect in any ASM contractile property can be linked to the manifestation of AHR. Evidence supporting these links in asthma is growing. Keywords: Adaptation, breathing, force, relaxation, shortening, stiffness, velocity.