The origin of airway hyperresponsiveness

Abstract

Consideration of the origin of airway hyperresponsiveness appears central to understanding the origin of asthma. Subjects with and without asthma differ both in the ease with which airway narrowing is produced by inhalation of histamine or methacholine and in the ability to demonstrate a maximal response to these agents. The latter appears, on present evidence, to be due to an added mechanism in asthma rather than the absence of a potent inhibitory process. Airway hyperresponsiveness is probably acquired during life as a result of airway reactions to various stimuli, although genetic factors such as atopy are likely to predispose the person to develop hyperresponsiveness. Environmental stimuli include inhaled allergens, chemical sensitizers, airway infections, immunization, and ozone. Allergen-induced airway hyperresponsiveness occurs in association with late-phase asthmatic responses. This and ozone-induced hyperresponsiveness have been demonstrated to be associated with release of chemical mediators and the cellular phase of inflammation. Their effect does not appear to be accounted for by increase in airway epithelial permeability, decrease in airway caliber, reflex bronchoconstriction, or beta-adrenoceptor blockade. The mechanism(s) responsible for the induced hyperresponsiveness are unknown but may involve airway epithelial damage, edema in and around the airway walls, stimulation of the noncholinergic excitatory or inhibition of the nonadrenergic inhibitory systems, or a change in function of airway smooth muscle. Airway hyperresponsiveness can be transient or persistent. Transient increases in responsiveness are almost certainly associated with mediator release and inflammation. It is not known whether persistent hyperresponsiveness is due to the same process, fired, for example, by leaky mediator-releasing cells and/or to some persisting change in neurogenic or smooth muscle function.