Airway inflammation and autonomic control.

Autonomic nerves control many aspects of airway function, including smooth muscle tone, epithelial cell function, mucus secretion, bronchial flow and permeability, and inflammatory mediator release. There is considerable evidence that there may be abnormalities of autonomic function in asthma, perhaps as a result of airway inflammation. Inflammatory mediators might stimulate bronchial afferent receptors (irritant receptors and C-fibre endings) to produce reflex cholinergic bronchoconstriction. Anticholinergic drugs have not proved to be very effective in controlling clinical asthma, however, suggesting that cholinergic reflex mechanisms may not play a major role. Adrenergic abnormalities have been described in asthma. There is no direct sympathetic neural control of airway smooth muscle, suggesting that circulating catecholamines may regulate airway tone, and counteract the effect of inflammatory mediators in asthma. Surprisingly, the concentration of adrenaline in plasma does not rise in asthmatic subjects with induced bronchoconstriction, or even during an acute asthma attack. The function of beta-adrenoceptors in asthma is uncertain, but there is some evidence that beta-receptor function may be impaired, possibly as a result of inflammatory mediator release. alpha-Adrenoceptor function may be enhanced in asthma; inflammatory mediators may 'turn on' bronchoconstrictor alpha-adrenergic responses in airway smooth muscle, and alpha-agonists may have a bronchoconstrictor effect in asthmatic subjects. But specific alpha-blockers have little effect on airway function, and the role of alpha-receptors in asthma is questionable. Non-adrenergic, non-cholinergic nerves are the only neural bronchodilator mechanism in human airways. The neurotransmitter has not yet been identified but vasoactive intestinal peptide (VIP) is a possible candidate.(ABSTRACT TRUNCATED AT 250 WORDS)