Λεξικό .. Asthma and autonomic abnormalities

The human airways are innervated via efferent and afferent autonomic nerves, which regulate many aspects of airway function. It has been suggested that neural control of the airways may be abnormal in asthmatic patients, and that neurogenic mechanisms may contribute to the pathogenesis and pathophysiology of asthma [1]. Τhe autonomic innervation of the human airways and possible abnormalities in asthma are discussed. The parasympathetic nervous system is the dominant neuronal pathway in the control of airway smooth muscle tone.

Stimulation of cholinergic nerves causes bronchoconstriction, mucus secretion, and bronchial vasodilation. Although abnormalities of the cholinergic innervation have been suggested in asthma, thus far the evidence for cholinergic dysfunction in asthmatic subjects is not convincing. Sympathetic nerves may control tracheobronchial blood vessels, but no innervation of human airway smooth muscle has been demonstrated. beta-Adrenergic receptors, however, are abundantly expressed on human airway smooth muscle and activation of these receptors causes bronchodilation.

The physiological role of beta-adrenergic receptors is unclear and their function seems normal in asthmatic patients. Inhibitory nonadrenergic noncholinergic (NANC) nerves, containing vasoactive intestinal peptide and nitric oxide, may be the only neural bronchodilator pathways in human airways. Although a dysfunction of inhibitory NANC nerves has been proposed in asthma, thus far no differences in inhibitory NANC responses have been found between asthmatics and healthy subjects. Excitatory NANC nerves, extensively studied in animal airways, have also been detected in human airways. In animal studies, stimulation of excitatory NANC nerves causes bronchoconstriction, mucus secretion, vascular hyperpermeability, cough, and vasodilation, a process called 'neurogenic inflammation'. Recent studies have demonstrated an interaction between the excitatory NANC nervous system and inflammatory cells. Neuropeptides may influence the recruitment, proliferation, and activation of leukocytes. On the other hand, inflammatory cells may modulate the neuronal phenotype and function. The functional relevance of the excitatory NANC nervous system and its interaction with the immune system in asthma still remains to be elucidated [1].

Studies of airway smooth muscle from non asthmatic patients have shown no correlation between in vivo and in vitro reactivity to histamine, suggesting that bronchial hyperreactivity, at least in chronic obstructive pulmonary disease, cannot be explained by an abnormality of airway smooth muscle, but is more likely to be a defect in autonomic control. This might be due to an exaggeration of excitatory mechanisms (cholinergic, ˜-adrenergic or non-cholinergic excitatory) or to a deficiency in inhibitory mechanisms (™-adrenergic or non-adrenergic inhibitory). Many studies have now examined the possibility that autonomic receptor function may be normal in asthma. Asthma has been recently redefined as a chronic desquamating eosinophilic bronchitis [2].

References

1. van der Velden VH, Hulsmann AR. Autonomic innervation of human airways: structure, function, and pathophysiology in asthma. Neuroimmunomodulation. 1999 May-Jun;6(3):145-59.

2. Marsac JH, Vlastos FD, Lacronique JG. Inhaled beta adrenergic agonists and inhaled steroids in the treatment of asthma. Ann Allergy. 1989 Sep;63(3):220-4