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Pneumologie 2011; 65(5): 283-292
DOI: 10.1055/s-0030-1256123
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Neuronale Kontrolle bei chronisch entzündlichen und obstruktiven Lungenerkrankungen wie Asthma bronchiale und COPD

Innervation of the Airways in Asthma Bronchiale and Chronic Obstructive Pulmonary Disease (COPD)Q.  T.  Dinh1 , 2 , H.  Suhling1 , A.  Fischer3 , A.  Braun4 , T.  Welte1
  • 1Zentrum für Innere Medizin, Medizinische Hochschule Hannover (MHH), Klinik für Pneumologie, Hannover (Leiter: Prof. Dr. T. Welte)
  • 2Charité Zentrum 12 für Innere Medizin und Dermatologie, Medizinische Klinik mit Schwerpunkt Psychosomatik, Charité – Universitätsmedizin Berlin, Freie Universität Berlin & Humboldt-Universität zu Berlin, Berlin (Leiter: Prof. Dr. B. F. Klapp)
  • 3Zentrum für Pädiatrie, Klinische Forschergruppe Allergologie, Charité – Universitätsmedizin Berlin, Freie Universität Berlin & Humboldt-Universität zu Berlin, Berlin (Leiter: Prof. Dr. A. Fischer)
  • 4Fraunhofer Institut für Toxikologie und Experimentelle Medizin (ITEM), Abteilung Immunologie, Allergologie und Immuntoxikologie, Hannover (Leiter: Prof. Dr. N. Krug)
Further Information

Publication History

eingereicht 27. 10. 2010

akzeptiert nach Revision 8. 12. 2010

Publication Date:
26 January 2011 (online)

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Zusammenfassung

Chronisch entzündliche Atemwegserkrankungen wie Asthma bronchiale und die chronisch obstruktive Lungenerkrankung (COPD) können nach den gegenwärtigen Forschungsergebnissen weder als eine rein immunologische noch als eine ausschließlich neuronale Erkrankung angesehen werden [1] [2]. Die entzündlichen Veränderungen werden von einer Vielzahl an immunologischen und neuronalen Mediatoren hervorgerufen und beeinflusst. Im Bereich der Pathophysiologie und Pathobiochemie des Asthma bronchiale sowie der COPD sind bereits über fünfzig Mediatoren mit verschiedenen Effekten verschiedenste pulmonale Funktionen beschrieben worden. Die Mediatoren werden dabei von Entzündungszellen, wie Mastzellen, Eosinophilen, Basophilen, Neutrophilen oder T-Lymphozyten, gebildet. Weiterhin gehören auch andere Zellen, wie Epithelzellen, Endothelzellen, Myozyten oder Atemwegsneurone, zu den Mediator-bildenden und freisetzenden Zellen. Neben den klassischen Mediatoren Noradrenalin in postganglionären sympathischen Nervenfasern und Acetylcholin in parasympathischen Nervenfasern existiert eine Reihe von Neuropeptiden, die ausgeprägte pharmakologische Effekte auf den Muskeltonus der Blutgefäße und der Bronchien, die Drüsenfunktion und auf Entzündungs- und Immunzellen hat. Diese Neuropeptide gehören zu keinem morphologisch eingrenzbaren System. Diese Neuropeptide werden unter dem Begriff des nicht-adrenergen nicht-cholinergen (NANC)-Systems zusammengefasst. Die Rolle des Nervensystems in Bezug auf die asthmatische oder chronisch obstruktive Erkrankung wurde bisher sehr unterschiedlich gewichtet und bewertet. Sehr früh begann man sich für das Nervensystem der menschlichen Lunge zu interessieren und es anatomisch detailliert zu beschreiben [3] [4] [5], da ein Zusammenhang zwischen dem Nervensystem und der Pathophysiologie des Asthma bronchiale und der COPD vermutet wurde. Seitdem wurden unterschiedliche Aspekte des Nervensystems untersucht. Etablierte Pharmakotherapiekonzepte mit Anticholinergika, wie Ipratropiumbromid (Atrovent®) oder Tiotropiumbromid (Spiriva®), bestehen darin, durch einen kompetitiven Antagonismus die Effekte des natürlichen Überträgerstoffes an den cholinergen Neuronen zu hemmen und damit die Erschlaffung der glatten Muskulatur der Bronchien zu erreichen. Die effektivsten Bronchodilatatoren sind die β2-Sympathomimetika (Sabutamol), welche effektiv die Freisetzung von Acetylcholin aus cholinergen Neuronen hemmen und gleichzeitig die β2-Rezeptoren an den motorischen Endplatten der Muskelzellen stimulieren. Dieser Wirkungsmechanismus führt zu einer Bronchodilatation durch Relaxation der glatten Muskulatur. Über die weitere Rolle des Nervensystems bei den chronisch obstruktiven Lungenerkrankungen des Menschen ist aber bisher nur wenig bekannt. Wegen der Komplexität der neuroimmunologischen Interaktion beim Asthma bronchiale und der COPD muss in Zukunft weitere Forschung zum Verständnis der Rolle der Atemwegsinnervation und deren Aktivierung und Interaktion mit Entzündungszellen unternommen werden. Dieser Artikel gibt eine Übersicht über die bisherigen Erkenntnisse der neuronalen Kontrolle der beiden großen obstruktiven Atemwegserkrankungen.

Abstract

Airway nerves have the capacity to control airway functions via neuronal reflexes and through neuromediators and neuropeptides. Neuronal mechanisms are known to play a key role in the initiation and modulation of airway hyperresponsiveness and inflammation. Therefore, the nerve fibres may contribute to airway narrowing in asthma and COPD. In addition to the traditional transmitters such as norepinephrine in postganglionic sympathetic nerve fibres and acetylcholine in parasympathetic nerve fibres, a large number of neuropeptides have been identified to have different pharmacological effects on the muscle tone of the vessels and bronchi, mucus secretion and immune cells. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and even cold, dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. Different aspects of the neurogenic inflammation have been well studied in animal models of chronic airway inflammation and anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium bromide (Spiriva®) have been proved to be important when used as bronchodilators for the treatment of obstructive airway diseases such as COPD. However, little is known about the role of neurogenic airway inflammation in human diseases. In this review, we address the current knowledge of the airway sensory nerves in human asthma and COPD.

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PD Dr. med. Quoc Thai Dinh

Klinik für Pneumologie
Leiter der Arbeitsgruppe:
Experimentelle Pneumologie und Allergologie
Medizinische Hochschule Hannover (MHH)

Carl-Neuberg-Str. 1
30625 Hannover

Email: Dinh.Quoc@mh-hannover.de

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