Review

Autonomic Innervation of Human Airways: Structure, Function, and Pathophysiology in Asthma
Vincent H.J. van der Velden^a,b, Anthon R. Hulsmann^c

Departments of
^aImmunology and
^bPulmonary Medicine, Erasmus University and University Hospital Dijkzigt and
^cDepartment of Pediatrics, Sophia Children's Hospital, Rotterdam, The Netherlands

Address of Corresponding Author

NeuroImmunoModulation 1999;6:145-159 (DOI: 10.1159/000026376)

  Key Words

• Autonomic innervation
• Airways
• Asthma
• Immunomodulation

  Abstract

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. In this review, the 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. -Adrenergic receptors, however, are abundantly expressed on human airway smooth muscle and activation of these receptors causes bronchodilation. The physiological role of -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.

  Author Contacts

V.H.J. van der Velden
Department of Immunology, Erasmus University
PO Box 1738, NL-3000 DR Rotterdam (The Netherlands)
Tel. +31 10 408 7192, Fax +31 10 436 7601
E-Mail vandervelden@immu.fgg.eur.nl

  Article Information

Received: Received: April 17, 1998
Accepted: May 28, 1998
Number of Print Pages : 15
Number of Figures : 2, Number of Tables : 1, Number of References : 266