In humans, almost all of the efferent autonomic nerves in the lungs are branches of the parasympathetic system derived from the vagus nerve, and are cholinergic in action (4). Branches of the vagus nerve travel along the airways and synapse at peribronchial ganglia with short postganglionic nerves, which supply airway smooth muscle cells, mucous glands, and possibly the ciliated epithelial cells, predominantly in the central airways. The release of acetylcholine from varicosities and terminals of the postgan-glionic nerves activates muscarinic receptors, thereby stimulating smooth muscle contraction, releasing mucus from mucous glands, and possibly accelerating ciliary beat frequency. At rest, a low level of cholinergic, vagal (bronchomotor) tone can be demonstrated in animals. This level of choli-nergic activity can be augmented by a variety of stimuli through neural reflex pathways (Fig. 1), resulting in rapid bronchoconstriction and release of mucus from airway mucous glands. Afferent activity can arise from irritant receptors and C fibers located anywhere in the upper and lower airways, and probably also from the esophagus and carotid bodies. Impulses due to receptor stimulation are transmitted along vagal afferents through the brain-stem vagal nuclei to vagal efferents ending mainly in the central airways. Stimuli to which these receptors respond include mechanical irritation; many irritant gases; aerosols; particles; cold, dry air; allergens; and specific mediators such as histamine and some eicosanoids (5,6). The bronchoconstriction that results from these stimuli is inhibitable by atropine. There is, thus, strong experimental evidence that airway caliber is at least partly under parasympathetic control. There is also clinical evidence that cholinergic bronchomotor tone is increased in both asthma (7) and COPD (8). These data provide the rationale for the use of anticho-linergic agents in airways diseases.
By competing with acetylcholine at muscarinic receptors, anticholiner-gic agents inhibit cholinergic activity, both tonic and phasic, and permit airways to dilate. However, the fact that airflow limitation is seldom completely
reversed by the use of anticholinergic agents in airways diseases suggests that cholinergic vagal activity probably accounts for only a part of the airflow obstruction in patients with asthma or COPD.
Anticholinergic agents do not affect the numerous other mechanisms of airway obstruction in asthma and COPD. They have been shown to have some anti-inflammatory properties in vitro (9,10); however, the relevance of these to their clinical use is uncertain at present.
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.