The Pathophysiology of Asthma: Smooth Muscle Spasm

For the purpose of this discussion, the pathophysiologic features of asthma will be divided into muscle spasm, airways inflammation with edema, and mucus hypersecretion. While all three are relatively constant features of asthma, their proportionate contribution to the abnormal physiology may vary considerably with the state of the disease. For example, smooth muscle spasm is probably the feature that accounts for rapid reversibility of the airways obstruction, while inflammatory edema and mucus plugging of the airways are more likely to account for the more slowly reversible or irreversible forms of the disorder.

Smooth Muscle

Smooth Muscle Spasm

In models of asthma, such as allergic bron-choconstriction in the guinea pig, the smooth muscle contraction is not associated with airway edema or mucus plugging of the airways so that this highly typical reaction can be assumed to be due solely to smooth muscle constriction. This contrasts sharply with human asthma deaths from asthma which are always associated with edema of the airway walls and mucus plugging of the airway lumen. This does not mean that smooth muscle spasm does not occur in chronic asthma, but only that its contribution to the overall airway obstruction may wane as the disease becomes more severe.

The airway smooth muscle is greatly influenced by the nervous system (Fig 1). The control comes both from the cholinergic system which constricts bronchial smooth muscle and the beta adrenergic system of nerves which relaxes bronchial smooth muscle. While the alpha adrenergic system contracts bronchial smooth muscle, these nerves are relatively sparse in the airways. The reaction is therefore due to circulating mediators acting on alpha adrenergic receptors in the smooth muscle. A third system of nerves, the so-called non-adrenergic inhibitory system, has been described more recently and this system, as its name suggests, is thought to relax the airway smooth muscle by an as yet unidentified mediator.

Several theories of asthma have developed which relate to one or another aspect of the neural control of the airway smooth muscle. One theory has stressed the possibility of a partial beta blockade, another abnormal cholinergic mechanism, and a third theory has suggested a basic abnormality of the non-adrenergic inhibitory system. Finally, it has also been suggested that airways of asthmatic subjects may be associated with smooth muscle that functions as a single unit so that the whole network contracts when part of it is stimulated.The smooth muscle contains readily identified mast cells and it seems likely that these cells are responsible for the fact that the muscle can be sensitized in vitro so that it will react to antigen challenge. The importance of mediator release from these mast cells in the normal control of smooth muscle is unclear at the present time, but it seems likely that they are important in allergically-mediated bronchoconstriction.


Figure1. Diagrammatic representation of the airway. We show that the smooth muscle is under neurogenic control where vagal stimulation constricts and beta adrenergic stimulation dilates the airways. The non- adrenergic relaxation mechanisms are shown as are the alpha adrenergic stimulating mechanisms, but these are less dear. The diagram shows that mast cell concentration increases from the epithelial lumen to the submucosa. (For further discussion, see text.)