Mechanisms of airway hyperresponsiveness.
Airway hyperresponsiveness (AHR) to direct (histamine and methacholine) and indirect (exercise, cold air, hyperventilation, AMP) challenges is a universal and defining feature of asthma. One component of AHR is transient or inducible and occurs after allergen exposure, for example, and improves occasionally rapidly after inhaled corticosteroids or environmental control. This transient airway hyperresponsiveness is more marked to the indirect stimuli. There are convincing data linking this component of AHR to airway inflammation; however, the precise mechanisms linking airway inflammation and hyperresponsiveness of the airway smooth muscle are not clear. The other component of AHR is more persistent and is relatively refractory to environmental control and inhaled corticosteroids. This is likely secondary to structural airway changes, which are collectively referred to as airway remodeling, and which are a result of the chronic (rather than the acute) effects of airway inflammation. This persistent AHR is best reflected by airway hyperresponsiveness to direct stimuli such as methacholine. The mechanisms are also uncertain, but reduced airway caliber, increased airway wall thickness, increased airway smooth muscle mass, and perhaps contractility likely all play a role.
Cockcroft
Donald W
DW
Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada. cockcroft@sask.usask.ca
Davis
Beth E
BE
D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D012137:Respiratory System / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*