Stimuli may lead to bronchoconstriction in a variety of ways, which we will briefly review. Factors causing hyperresponsiveness can be separated into prejunctional and postjunctional. Prejunctional mechanisms are those related to amplification of bronchoconstrictor stimuli; they potentially lead to a leftward shift of the in vivo dose response curve and are thus associated with hypersensitivity. Postjunctional factors amplify the bronchoconstrictor response. This potentially leads to an increased maximal response and hence to excessive airway narrowing.
Pre- and postjunctional factors contribute to hyperresponsive lower airways. Muscle contraction and mucus secretion can accompany hypertrophy and hyperplasia of smooth muscle cells and glandular structures. Vascular congestion, edema, cellular infiltration and collagen deposition beneath the airway wall can contribute to airway narrowing.
These phenomena do not clarify what is cause and what is effect in bronchial hyperresponsiveness. There is no convincing evidence that the primary defect is in the smooth muscle cells, the autonomic nervous system, mast cells or the other elements in the airways [1] or that known defects are not secondary to the inflammatory process. There is increasing evidence for an immunological disorder, associated with increased number and activity of Th2 lymphocytes. The airways may only be the target organ for an abnormal immune response.
The pathophysiological framework presented int the above illustration is useful for understanding hyperresponsiveness. Next we will examine how initial airway geometry affects the response as measured in vivo.
1. Barnes PJ. Neural control of the human airways. Am Rev Respir Dis 1986;134:1289-1314.