Airway Hyperresponsiveness in Asthma: A Better Understanding Yet to Yield Clinical Benefit

Abstract

Airway inflammation and hyperresponsiveness (AHR) are important features of asthma. Both inflammation and AHR are complex traits that can each originate from a plethora of factors, where every factor can be independent, interconnected and dispensable. This review examines the complexity of the indices that we use to assess airway responsiveness. These indices entail intricate information regarding the individual and the combined dynamic behavior of all the airways that constitute the tracheobronchial tree during the activation of airway smooth muscle (ASM). Because many factors other than ASM contractility can influence airway narrowing, the defects responsible for the manifestation of AHR are difficult to infer. New tests and technologies are being developed to decipher the meaning of the indices of airway responsiveness and have already leaped forward our understanding of AHR. This review also gives prominence to the concept of ASM plasticity.ASM mass and contractile capacity is not fixed over time. Several facets of inflammation can increase ASM force indirectly over a prolong period of time by causing tissue damage and repair, which ultimately leads of airway wall remodeling that embodies an enlargement of ASM mass. This could contribute to the fixed component of AHR. The gain of force due to inflammation can also be transient and conditional to the presence of inflammatory mediators that are capable of increasing the contractile capacity of ASM. This could contribute to the variable, and more readily modifiable, component of AHR. We are now aware that a multitude of muscle and non-muscle factors can contribute to AHR within an asthmatic individual, and that these factors are often times distinct between individuals. Consequently, the relative contribution of a single factor within a group of patients is usually very small. This is the reason why our ever-growing understanding of AHR in asthma does not quite yet avail patients.