title: Airway hyperresponsiveness; smooth muscle as the principal actor.
abstract: Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway.
authors.affiliation: Meakins-Christie Laboratories, McGill University Health Center Research Institute, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lauzon
authors.affiliation: Meakins-Christie Laboratories, McGill University Health Center Research Institute, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
keywords: Airway epithelium; Airway hyperresponsiveness; asthma; smooth muscle