Airway hyperresponsiveness can be defined as exaggerated airway narrowing in response to a wide variety of stimuli. 1 Boushey HA Holtzman M Sheller JR Nadel JA Bronchial hyperractivity: state of the art.. Am Rev Respir Dis. 1980; 121: 389-413 PubMed Google Scholar Some of these stimuli are listed in Table 1. These include endogenous mediators such as acetylcholine, histamine, leukotrienes, prostaglandins and bradykinin, and also exogenous stimuli, many of which are involved in producing clinical exacerbations in patients with asthma. Physicians are interested in airway hyperresponsiveness because this phenomenon helps to explain many of the clinical manifestations of asthma. Figure 1 shows a wiring diagram of airway smooth muscle. This diagram points out that stimuli deposited in the airway lumen can cause contraction of this muscle by a number of different pathways, probably the least important of which is direct effects on the muscle. The muscle sits at some distance from the airway lumen, and before contacting the muscle, any stimulus put into the lumen comes in contact with several other cells. These include mast cells and eosinophils that are present in the lumen, in the airway epithelium and in the vicinity of nerves and muscle. They also include macrophages, the most populous free cell in the airway lumen. By far the largest number of cells in the airway lumen are airway epithelial cells which themselves have the potential for releasing mediators, when stimulated, that can effect the behavior of airway smooth muscle. There also is the potential for recruitment of new cells and mediators from the blood vessels. For a long time it was thought that the only significant neural pathway for contraction of airway smooth muscle was the reflex that had its efferent limb in the parasympathetic fibers of the vagus nerve. It is clear that another important pathway involves release of mediators from afferent nerves themselves. Finally, airway smooth muscle cells can be contracted by direct stimulation of receptors present on their surface. Table 1Stimuli that Cause Exaggerated Airway Narrowing in Patients with Airway Hyperresponsiveness Endogenous Mediators Exogenous Stimuli Acetylcholine Dry Air (Exercise) Histamine Sulfur Dioxide Leukotrienes (C4, D4, E4) Acid Aerosols Prostaglandins (D2, F2) Hypotonic and Hypertonic Aerosols Bradykinin Open table in a new tab