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Asthma pp 127-149 | Cite as

Theophylline in the management of asthma: time for a reappraisal?

  • M. Weinberger

Summary

Theophylline is the oldest medication still in routine use for the treatment of asthma. Used initially as a parenteral medication for acute bronchodilatation, theophylline’s primary value today results from its high degree of efficacy as a maintenance medication for preventing symptoms of chronic asthma when administered in doses that maintain serum concentrations between 10 and 20 µg/mL Moreover, these doses that provide optimal efficacy are generally well tolerated so long as initial doses are low, increased only slowly, and serum concentration do not exceed 20 µg/ml. While newer medications have added substantially to our therapeutic armamentarium for treatment of asthma, theophylline continues to fill an important niche as the most effective oral maintenance medication and the only maintenance medication to have substantial additive effect with inhaled corticosteroids. Inhaled β-2-agonists, such as salbutamol, have improved intervention for acute symptoms but failed as reliable and safe maintenance medication. The newer longer acting agents of this class, such as salmeterol, have greater potential for use as a maintenance medication but concerns persist regarding tolerance during long term therapy. Cromolyn and nedocromil have been enthusiastically embraced by some clinicians, but a critical examination finds them weakly potent and inconvenient to use because of requirements for 4 times daily therapy. Moreover, whereas theophylline has substantial clinically important additive effects with inhaled corticosteroids, cromolyn and nedocromil do not. The empirical evidence for the clinical efficacy of theophylline as maintenance medication has recently been given additional mechanistic support by the demonstration that theophylline has anti-inflammatory in addition to bronchodilator effect. Nonetheless, it is the empirical data in the form of controlled clinical studies that provide the basis for continued use of theophylline as maintenance medication for chronic asthma. It’s justifiable role is as an alternative to low dose inhaled corticosteroids as monotherapy for milder chronic asthma or as an additive maintenance medication to inhaled corticosteroids when needed.

Keywords

Allergy Clin Immunol Sodium Cromoglycate Maintenance Medication Chronic Asthma Cromolyn Sodium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Zusammenfassung

Theophyllin bei der Behandlung des Asthmas: Zeit für eine Neubewertung? Theophyllin ist die älteste Medikation, welche bei der Behandlung des Asthmas noch immer routinemäßig verwendet wird. Seine klinische Wirksamkeit wurde erstmals von Doktor Samson Hirsch (1922) in der deutschen Literatur demonstriert. Er behandelte zwei Asthmatiker damit und erzielte einen therapeutischen Erfolg, der den anderen zu dieser Zeit verfügbaren Medikamenten überlegen war. In den späten 30er Jahren wird in der medizinischen Literatur die intravenöse Theophyllintherapie bei akutem, epinephrinrefratärem Asthma beschrieben. Orale Theophyllinpräparate in fixer Dosiskombination mit Ephedrin wurden zur Standardbehandlung durch über 30 Jahre verwendet, nachdem die Wirksamkeit dieser Kombination in den 40er Jahren dokumentiert worden war.

Seit diesen frühen Berichten haben der massive Gebrauch von spezifischen Beta-2-Agonisten auf dem inhalativen Weg, kombiniert mit früher systemischer Kortikosteroidtherapie, den Routinegebrauch von intravenösem Theophyllin für die meisten Patienten mit akutem Asthma unnötig gemacht.

Im Gegensatz dazu bleibt die klinische Indikation für die oralen Theophylline bestehen, obwohl in stark veränderter Form seit den Berichten von Brown (1940). In einer 1974 erschienenen Publikation wurde gezeigt, daß die Kombination von Ephedrin und Theophyllin nur in puncto Toxizität synergistisch wirkte, ohne klinisch relevante additive Effekte. In dieser Arbeit wurde aber auch aufgezeigt, daß Theophyllin in einer Dosierung, welche eine Serumkonzentration von über 10 µg/ ml erbrachte, besonders bei Kindern die Symptomatik erfolgreich verminderte und die Episoden von Notfallstherapie bei Kindern mit schwerem chronischen Asthma reduzierte. Die halbe Dosis, welche damals noch immer als hochdosierte Therapie angesehen wurde, hatte bei diesen Kindern einen Effekt, der nur wenig vom Placebo abwich. Darüberhinaus wurden die höheren Dosierungen gut vertragen, solang eine Serumkonzentration von 20 µg/ml nicht überschritten wurde.

In der Folge haben weitere Arbeiten die große therapeutische Sicherheit und Wirkung des Theophyllins als Erhaltungsmedikation für das chronische Asthma erwiesen, solange die Dosis durch die Messung des Serumspiegels sorgsam titriert und überwacht wird. Neuere Medikationen haben beträchtlich zu unserem therapeutischen Armamentarium in der Behandlung des Asthmas beigetragen, wie die langwirkende Beta-2-Mimetika. Diese haben zwar eine unzweifelhafte Bedeutung in der Erhaltungsmedikation erlangt, doch gibt es gewisse Vorbehalte, wenn keine begleitende inhalative Kortikosteroidtherapie stattfindet.

Cromoglykat und Nedocromil haben zwar keinen sicheren additiven Effekt, wenn sie mit inhalativen Kortikosteroiden verabreicht werden, doch ist ein solcher für Theophyllin sehr wohl nachgewiesen worden.

Die klinische Wirksamkeit des Theophyllins als Erhaltungstherapie wurde erst kürzlich durch den Nachweis der antientzündlichen Wirkung zusätzlich zum bronchodilatatorisehen Effekt unterstützt. Nichtsdestoweniger sind es noch immer die Daten aus kontrollierten klinischen Studien, welche die Basis für eine Fortsetzung des Gebrauches von Theophyllin als Erhaltungstherapie beim chronischen Asthma bilden. Es erscheint gerechtfertigt, die Theophyllintherapie als Alternative zur niedrigdosierten inhalativen Kortikosteroidtherapie in Form einer Monotherapie beim milden chronischen Asthma zu verwenden, oder, wenn nötig, als eine zusätzliche Erhaltungsmedikation bei inhalativer Kortikosteroidbehandlung.

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Copyright information

© Springer-Verlag/Wien 1995

Authors and Affiliations

  • M. Weinberger
    • 1
  1. 1.Department of PediatricsUniversity of Iowa Hospital and ClinicsIowa CityUSA

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