Summary
To investigate whether endogenous transmitters play a role in different forms of bronchial asthma we determined histamine and noradrenaline plasma levels as well as airway resistance (Rt) before and after exercise and allergen challenge in children. The study demonstrates that in exercise induced asthma (EIA) broncho-constriction was paralleled by increases of noradrenaline, but not of histamine plasma levels. This increase of noradrenaline was much more pronounced than that observed in the asthmatic control group not suffering from EIA. In contrast to what has been observed in EIA, bronchoconstriction in response to allergen challenge was closely associated with increases of histamine, but not of noradrenaline plasma levels. Between histamine concentrations and severity of illness a good correlation was found (r=0.98).
Tests carried out after oral administration of theophylline showed a protection against EIAand allergic induced asthma. Since theophylline in allergic asthma concomitantly reduced the increase in Rt and plasma histamine it is suggested that at least part of the beneficial effects of theophylline in allergic asthma may result from inhibition of histamine release. In those children suffering from EIA theophylline did not affect noradrenaline release. Thus, consideration must be given to effects of theophylline against EIA which are based on other mechanisms. Whether these effects are solely attributable to relaxation of bronchial smooth muscle or not remains to be clarified.
In conclusion this study clearly has identified exercise and allergic induced asthma as different types of the syndrome that we call asthma. Drugs which prevent against both types may do this by different modes of action.
Zusammenfassung
Um zu untersuchen, ob endogene Transmitter bei der Auslösung und Unterhaltung verschiedener Formen des Asthma bronchiale eine Rolle spielen, haben wir bei Kindern vor und nach einer Laufbelastung sowie vor und nach einer inhalativen Provokation mit wäßrigen Allergenextrakten das Serumhistamin, Serumnoradrenalin und den bronchialen Strömungswiderstand (Rt) bestimmt. Die Untersuchung zeigt, daß das Belastungsasthma mit einem starken Anstieg des Plasmanoradrenalins, nicht jedoch des Plasmahistamins einhergeht. Dieser Anstieg war wesentlich ausgeprägter als der bei einem asthmatischen Vergleichskollektiv ohne Anstrengungsasthma. Im Gegensatz dazu zeigten die Kinder, die nach einer Allergenprovokation einen Asthmaanfall entwickelten, einen signifikanten Histamin-, jedoch keinen Noradrenalinanstieg. Zwischen Histamin-Serumspiegel und Stärke der Bronchokonstriktion bestand eine gute Korrelation (r=0.98).
Nach oraler Applikation übte Theophyllin einen Schutz sowohl gegenüber dem Anstrengungsasthma, als auch gegenüber dem allergisch bedingten Asthma aus. Da Theophyllin beim allergisch ausgelösten Asthma nicht nur zu einem Abfall von Rt führte, sondern auch den Histaminanstieg verminderte, kann vermutet werden, daß ein Teil der Wirkung dieser Substanz beim allergischen Asthma auf einer Hemmung der Histaminfreisetzung beruht. Die Noradrenalinfreisetzung beim Anstrengungsasthma beeinflußte es nicht. Für seine protektive Wirkung bei dieser Asthmaform müssen daher andere Wirkungsmechanismen angenommen werden. Ob diese ausschließlich auf einer Relaxation beruhen, muß ungeklärt bleiben.
Als Schlußfolgerung dieser Untersuchung wird deutlich, daß das Anstrengungsasthma und das allergische Asthma 2 verschiedene Typen eines Syndroms sind. Arzneimittel, die gegenüber beiden Typen wirksam sind, können dies über verschiedene Wirkungsmechanismen tun.
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Dedicated to Prof. Dr. G.-A. von Harnack in occasion of his 65th birthday
Supported by a grant from the Ministerium für Wissenschaft und Forschung, NRW
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Reinhardt, D., Becker, B., Nagel-Hiemke, M. et al. The role of histamine and noradrenaline in allergic and exercise induced asthma of childhood, and the effect of theophylline treatment. Klin Wochenschr 60, 919–925 (1982). https://doi.org/10.1007/BF01716948
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DOI: https://doi.org/10.1007/BF01716948